SHANK3

[Aneta Molenda]

Dear,

What transcript and c./p. nomenclature would you use for the sequence change below (in SHANK3 gene). There appears to be c.p. nomenclature inconsistencies between different websites (e.g. Ensembl, Blat, Franklin, Mutalyzer) for the same transcript. Is it possible to somehow incorporate this information.

1.       1. NM_033517.1 on Ensembl ENST00000262795

 Ensembl Build 37

ENST00000262795.3 c.2959   aa 987

Blat on build 37 is showing aa 838 (as build 38 - Ensembl)

Franklin build 37

ENST00000262795.3 Exon 22 | c.2959del | p.Val987Trpfs*107 chr22-51159171 CG>C

Ensembl build 38

ENST00000262795.8 SHANK3-201 c.2512  aa 838 chr22-50720743 CG>C

Exon 20 | c.2512del | p.Val838Trpfs*107

Franklin + Ensemble + Blat – the same aa

NM_033517.1 is not in gbk file from NCBI

2. NM_001080420

NM_001080420.1 (SHANK3) corresponds with DECIPHER.

NM_001080420.1: The RefSeq was permanently suppressed

3. NM_001372044.2

Build 38

From NCBI: On NC_000022.11 of the GRCh38.p14 assembly, the SHANK3 gene locus is missing 36 GC-rich nucleotides near the 5' end of exon 12 of transcript NM_001372044.2 and also has a CG deletion in exon 2 which cause a frameshifted ORF. These assembly sequencing errors are corrected in GRCh38.p14 assembly patch sequence NW_015148969.2. The MANE Select annotation is on this patch sequence NW_015148969.2. 

Franklin build 38

NM_001372044.2 chr22-50720743 CG>C build 38 Exon 22 | c.3136del | p.Val1046Trpfs*107

But c.3097 Val1033 using Blat

ENST00000692848.2 build 38

Ensembl c.3094 Val1032 not consistent either with Blat or Franklin

Build 37:

NM_001372044.2 Exon 22 | c.3136del | p.Val1046Trpfs*107 on Franklin (1033 on Blat)

 

Mutalyzer :

GRCh38(chr22):50720744del

NC_000022.11(NM_033517.1):c.2872del

NC_000022.11(NM_001372044.2):c.3097del

NC_000022.11(NM_001372044.1):c.3097del

GRCh37(chr22):51159172del

NC_000022.10(NM_001372044.2):c.3097del

NC_000022.10(NM_001372044.1):c.3097del

 

                Thank you

                             Aneta Molenda

 

[Johan den Dunnen]

Dear Aneta,

unfortunately, I will not be able to answer your questions. You should ask the developers of the Ensembl, Blat, Franklin, and Mutalyzer tools how they get to the variant descriptions they give.

What I do see is that you use descriptions like GRCh38(chr22):50720744del. Please note this is not correct. Following HGVS nomenlcature you should use NC_000022.11:g.50720744del. Note also that following HGVS nomenclature variants must be described at genomic level, descriptions at transcript, RNA and protein level may be added.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op vrijdag 19 december 2025 om 15:11:47 UTC+1 schreef Aneta Molenda: