rs147376000
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_017433.5(MYO3A):āc.4465A>Gā(p.Ile1489Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,613,820 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.4465A>G | p.Ile1489Val | missense_variant | 32/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.4465A>G | p.Ile1489Val | missense_variant | 32/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1777-18612A>G | intron_variant | 1 | |||||
MYO3A | ENST00000647478.1 | c.*1420A>G | 3_prime_UTR_variant, NMD_transcript_variant | 28/30 |
Frequencies
GnomAD3 genomes AF: 0.00519 AC: 790AN: 152152Hom.: 4 Cov.: 31
GnomAD3 exomes AF: 0.00532 AC: 1337AN: 251330Hom.: 6 AF XY: 0.00544 AC XY: 739AN XY: 135846
GnomAD4 exome AF: 0.00650 AC: 9496AN: 1461550Hom.: 45 Cov.: 31 AF XY: 0.00639 AC XY: 4643AN XY: 727086
GnomAD4 genome AF: 0.00519 AC: 790AN: 152270Hom.: 4 Cov.: 31 AF XY: 0.00556 AC XY: 414AN XY: 74456
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 26, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | MYO3A: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 30 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 06, 2023 | - - |
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. - |
not specified Benign:2
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 | Jan 21, 2014 | Ile1489Val in Exon 32 of MYO3A: This variant is not expected to have clinical si gnificance because it has been identified in 0.6% (50/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs147376000). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at