rs116833707
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):c.9181G>A(p.Glu3061Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E3061E) has been classified as Likely benign.
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 | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.9181G>A | p.Glu3061Lys | missense_variant | 54/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.9184G>A | p.Glu3062Lys | missense_variant | 52/64 | ||
MYO15A | XM_017024714.3 | c.9121G>A | p.Glu3041Lys | missense_variant | 51/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.9181G>A | p.Glu3061Lys | missense_variant | 54/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000783 AC: 119AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 46AN: 249540Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135396
GnomAD4 exome AF: 0.0000930 AC: 136AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.0000756 AC XY: 55AN XY: 727234
GnomAD4 genome ? AF: 0.000782 AC: 119AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.000968 AC XY: 72AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 11, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 14, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 11, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Glu3061Lys va riant in MYO15A has been previously reported by our laboratory in two individual s with hearing loss, but a variant affecting the second copy of the gene was not identified in either individual. This variant has been identified in 0.28% (66/ 23988) of African chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org; dbSNP rs116833707). Although this variant has been s een in the general population, its frequency is not high enough to rule out a pa thogenic role. Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Glu3061Lys variant is uncertain, its frequen cy in the general population suggests that it is more likely to be benign. ACMG/ AMP Criteria applied: BS1_Supporting. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at