rs35575696
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM5BP4_StrongBP6BS1BS2
The NM_017433.5(MYO3A):c.3859C>A(p.Pro1287Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,124 control chromosomes in the GnomAD database, including 118 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1287R) 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 -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.3859C>A | p.Pro1287Thr | missense_variant | 30/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.3859C>A | p.Pro1287Thr | missense_variant | 30/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1777-37720C>A | intron_variant | 1 | |||||
MYO3A | ENST00000647478.1 | c.*1393+3584C>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00816 AC: 1241AN: 152128Hom.: 8 Cov.: 33
GnomAD3 exomes AF: 0.00929 AC: 2332AN: 251140Hom.: 17 AF XY: 0.0101 AC XY: 1371AN XY: 135780
GnomAD4 exome AF: 0.0109 AC: 15993AN: 1461878Hom.: 110 Cov.: 73 AF XY: 0.0111 AC XY: 8102AN XY: 727232
GnomAD4 genome ? AF: 0.00814 AC: 1240AN: 152246Hom.: 8 Cov.: 33 AF XY: 0.00826 AC XY: 615AN XY: 74422
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | MYO3A: BP4, BS1, BS2 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Pro1287Thr in Exon 30 of MYO3A: This variant is not expected to have clinical si gnificance because it has been identified in 1.0% (72/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs35575696). - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 22, 2020 | - - |
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