rs377389290
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):c.8816G>A(p.Arg2939His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000921 in 1,606,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.8816G>A | p.Arg2939His | missense_variant | 51/66 | ENST00000647165.2 | NP_057323.3 | |
MYO15A | XM_017024715.3 | c.8819G>A | p.Arg2940His | missense_variant | 49/64 | XP_016880204.1 | ||
MYO15A | XM_017024714.3 | c.8756G>A | p.Arg2919His | missense_variant | 48/63 | XP_016880203.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000167 AC: 40AN: 239232Hom.: 0 AF XY: 0.000160 AC XY: 21AN XY: 131084
GnomAD4 exome AF: 0.0000922 AC: 134AN: 1454022Hom.: 0 Cov.: 33 AF XY: 0.0000967 AC XY: 70AN XY: 723734
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 07, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.8816G>A (p.R2939H) alteration is located in exon 51 (coding exon 50) of the MYO15A gene. This alteration results from a G to A substitution at nucleotide position 8816, causing the arginine (R) at amino acid position 2939 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive nonsyndromic hearing loss 3 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 02, 2016 | p.Arg2939His in exon 51 of MYO15A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, the Egyptian jerboa, aardvark, and platypus have a histidine (His) at t his position despite high nearby amino acid conservation. It has been identified in 4/16426 of South Asian chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org; dbSNP rs377389290). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at