rs183256997
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016239.4(MYO15A):c.4779+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,593,516 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016239.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00212 AC: 323AN: 152268Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00236 AC: 505AN: 214016Hom.: 2 AF XY: 0.00228 AC XY: 265AN XY: 116390
GnomAD4 exome AF: 0.00330 AC: 4751AN: 1441130Hom.: 12 Cov.: 32 AF XY: 0.00329 AC XY: 2351AN XY: 715552
GnomAD4 genome AF: 0.00212 AC: 323AN: 152386Hom.: 1 Cov.: 33 AF XY: 0.00199 AC XY: 148AN XY: 74526
ClinVar
Submissions by phenotype
not provided Benign:3
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MYO15A: BS2 -
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Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1Benign:1
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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:2
4779+9G>A in Intron 15 of MYO15A: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.4% (27/6820) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS). -
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MYO15A-related disorder Benign:1
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