rs151254539
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017433.5(MYO3A):āc.1828A>Gā(p.Ile610Val) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I610T) has been classified as Uncertain significance.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.1828A>G | p.Ile610Val | missense_variant | 18/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.1828A>G | p.Ile610Val | missense_variant | 18/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1776+24045A>G | intron_variant | 1 | |||||
MYO3A | ENST00000642197.1 | n.2032A>G | non_coding_transcript_exon_variant | 18/27 | |||||
MYO3A | ENST00000647478.1 | c.1777-4671A>G | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152214Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000251 AC: 63AN: 251216Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135766
GnomAD4 exome AF: 0.000222 AC: 324AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.000217 AC XY: 158AN XY: 727196
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152332Hom.: 0 Cov.: 31 AF XY: 0.0000940 AC XY: 7AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 15, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYO3A protein function. ClinVar contains an entry for this variant (Variation ID: 445495). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs151254539, gnomAD 0.1%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 610 of the MYO3A protein (p.Ile610Val). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 22, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Autosomal recessive nonsyndromic hearing loss 30 Uncertain:2
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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.1828A>G (p.I610V) alteration is located in exon 18 (coding exon 16) of the MYO3A gene. This alteration results from a A to G substitution at nucleotide position 1828, causing the isoleucine (I) at amino acid position 610 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at