rs142823078
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_017433.5(MYO3A):āc.2705A>Cā(p.Asn902Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,590,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017433.5 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 |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.2705A>C | p.Asn902Thr | missense_variant | 24/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.2705A>C | p.Asn902Thr | missense_variant | 24/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1776+57237A>C | intron_variant | 1 | |||||
MYO3A | ENST00000642197.1 | n.2909A>C | non_coding_transcript_exon_variant | 24/27 | |||||
MYO3A | ENST00000647478.1 | c.*700A>C | 3_prime_UTR_variant, NMD_transcript_variant | 22/30 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000592 AC: 148AN: 250066Hom.: 0 AF XY: 0.000510 AC XY: 69AN XY: 135324
GnomAD4 exome AF: 0.000263 AC: 379AN: 1438704Hom.: 0 Cov.: 29 AF XY: 0.000244 AC XY: 175AN XY: 717006
GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74378
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 19, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Asn902Thr var iant in MYO3A has not been previously reported in individuals with hearing loss, but has been identified in 0.1% (50/62846) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs142823078 ) and 0.8% (3/400) of Ashkenazi Jewish control chromosomes by the Deafness Varia tion Database (http://deafnessvariationdatabase.org/). Although this variant has been seen in the general population, its frequency is not high enough to rule o ut a pathogenic role. Computational prediction tools and conservation analysis s uggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Asn902Thr variant is uncertain, these data suggest that it is more likely to be benign. - |
Autosomal recessive nonsyndromic hearing loss 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at