chr17-18173833-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):c.10403G>A(p.Arg3468Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000294 in 1,613,318 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3468W) has been classified as Likely benign.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.10403G>A | p.Arg3468Gln | missense_variant | 65/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.10406G>A | p.Arg3469Gln | missense_variant | 63/64 | ||
MYO15A | XM_017024714.3 | c.10343G>A | p.Arg3448Gln | missense_variant | 62/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.10403G>A | p.Arg3468Gln | missense_variant | 65/66 | NM_016239.4 | P1 | ||
ENST00000577847.1 | n.393-1088C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000601 AC: 149AN: 248118Hom.: 0 AF XY: 0.000682 AC XY: 92AN XY: 134940
GnomAD4 exome AF: 0.000287 AC: 420AN: 1460976Hom.: 1 Cov.: 29 AF XY: 0.000315 AC XY: 229AN XY: 726820
GnomAD4 genome AF: 0.000361 AC: 55AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74498
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2021 | - - |
Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 24, 2015 | p.Arg3468Gln in exon 65 of MYO15A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, 6 mammals (including mouse, rat, and hedgehog) have a glutamine (Gln) at this position despite high nearby amino acid conservation. In addition, computa tional prediction tools do not suggest a high likelihood of impact to the protei n. It has also been identified in 0.3% (21/8552) of East Asian chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs20 0456053). - |
MYO15A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at