rs33947968
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017433.5(MYO3A):c.2497G>T(p.Ala833Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,591,708 control chromosomes in the GnomAD database, including 5,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A833P) has been classified as Uncertain significance.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.2497G>T | p.Ala833Ser | missense_variant | 22/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.2497G>T | p.Ala833Ser | missense_variant | 22/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1776+48844G>T | intron_variant | 1 | |||||
MYO3A | ENST00000642197.1 | n.2701G>T | non_coding_transcript_exon_variant | 22/27 | |||||
MYO3A | ENST00000647478.1 | c.*492G>T | 3_prime_UTR_variant, NMD_transcript_variant | 20/30 |
Frequencies
GnomAD3 genomes AF: 0.0611 AC: 9295AN: 152096Hom.: 368 Cov.: 32
GnomAD3 exomes AF: 0.0637 AC: 15940AN: 250250Hom.: 678 AF XY: 0.0646 AC XY: 8745AN XY: 135286
GnomAD4 exome AF: 0.0781 AC: 112399AN: 1439494Hom.: 4930 Cov.: 30 AF XY: 0.0770 AC XY: 55262AN XY: 717456
GnomAD4 genome AF: 0.0610 AC: 9291AN: 152214Hom.: 368 Cov.: 32 AF XY: 0.0597 AC XY: 4444AN XY: 74414
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ala833Ser in Exon 22 of MYO3A: This variant is not expected to have clinical sig nificance because it has been identified in 9.0% (631/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs33947968). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal recessive nonsyndromic hearing loss 30 Benign:2
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at