rs761670755
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):āc.467T>Cā(p.Val156Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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).
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.467T>C | p.Val156Ala | missense_variant | 2/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.467T>C | p.Val156Ala | missense_variant | 2/66 | NM_016239.4 | P1 | ||
MYO15A | ENST00000583079.1 | n.100T>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 25AN: 239262Hom.: 0 AF XY: 0.0000683 AC XY: 9AN XY: 131850
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1459930Hom.: 0 Cov.: 36 AF XY: 0.0000289 AC XY: 21AN XY: 726294
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 19, 2016 | The p.Val156Ala variant in MYO15A has not been previously reported in individual s with hearing loss. It has been identified in 3/11266 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs761 670755). Although this variant has been seen in the general population, its freq uency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analyses suggest that the p.Val156Ala variant may not i mpact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Val156Ala variant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | The c.467T>C (p.V156A) alteration is located in exon 2 (coding exon 1) of the MYO15A gene. This alteration results from a T to C substitution at nucleotide position 467, causing the valine (V) at amino acid position 156 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at