chr10-25952223-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017433.5(MYO3A):c.113T>C(p.Val38Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000744 in 1,612,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V38L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.113T>C | p.Val38Ala | missense_variant | 3/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.113T>C | p.Val38Ala | missense_variant | 3/35 | NM_017433.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000957 AC: 24AN: 250902Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135614
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1460632Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 726638
GnomAD4 genome ? AF: 0.000374 AC: 57AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2023 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 38 of the MYO3A protein (p.Val38Ala). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1199644). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs144518447, gnomAD 0.1%). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 10, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2023 | The c.113T>C (p.V38A) alteration is located in exon 3 (coding exon 1) of the MYO3A gene. This alteration results from a T to C substitution at nucleotide position 113, causing the valine (V) at amino acid position 38 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive nonsyndromic hearing loss 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 11, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at