Doubt about variant nomenclature

[Alejandro Soriano]

Hi.

I have recently detected an insertion of a transposable element in the
intron of a gene. I have a doubt regarding how I should name this
variant since the inserted element shares a high homology with a LINE-1
but its sequence is not 100 % identical, therefore I cannot really
specify genomic coordinates. How should I name the insertion? Shoul I
submit the sequence to a database so that they can give it an accession
number?

Thanks in advance.

Best,

--
Alejandro Soriano Sexto
PhD Student
Centro de Biología Molecular Severo Ochoa (CBMSO)
Universidad Autónoma de Madrid (UAM), 28049
Madrid, Spain

[Johan den Dunnen]

Dear Alejandro,

there are two options;

1) you submit the variant sequence to a database like GenBank and use the accession.version number to describe the variant. Something like NC_0000mm.n:g.A_Bins[xxxxxxx.y:g.23_3500], assuming NC_0000mm.n is the genomic reference seuence, xxxxxxx.y is the accession.version number you receive and g.23 to g.3500 the sequence that is inserted.

2) you describe the differences between the inserted and the reference LINE-1 sequence, something like NC_0000mm.n:g.A_Bins[NC_0000pp.q:g.C_D;A;E_F;CGT;G_H], assuming NC_0000mm.n is the genomic reference seuence, NC_0000pp.q is the genomic reference sequence of the LINE-1 and g.C_D;A;E_F;CGT;G_H a description of the reference and its variants.

In general, option 1) gives a shorter and simpler description of the variant and is the preferred option.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)
http://www.HGVS.org/varnomen

Op woensdag 29 mei 2024 om 17:14:17 UTC+2 schreef Alejandro Soriano:

[Alejandro Soriano]

Dear Johan,

I have already uploaded the inserted sequence to GeneBank. The reference number I have obtained is the following: (GenBank: PP887427.1). When I try to check the nomenclature of the variant in VariantValidator I am naming the change as: 
NM_021957.4:c.1300_1301insPP887427.1 but it gives me an error (Char 26: Syntax error). I cannot find the reason why the nomenclature of this change is wrong, could you help me with that?

Thank you in advance.

Best regards,

Alejandro.

[Johan den Dunnen]

Dear Alejandro,

a correct description is like NM_021957.4:c.1300_1301ins[PP887427.1:g.1_1518], so indicating which nucleotides from PP887427.1 were inserted (I assumed that all nucleotides were inserted). As far as I know VariantValidator is not yet able to check this type of variant description. You could also try Mutalyzer (www.mutalyzer.nl), it was down when I wanted to try it.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op vrijdag 3 januari 2025 om 11:39:32 UTC+1 schreef Alejandro Soriano:

[Alejandro Soriano]

Dear Johan,

Thank you very much for your help! Really appreciate it.

Best regards,

Alejandro.