rs571886925
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_016239.4(MYO15A):c.264G>A(p.Thr88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 1 hom. )
Consequence
MYO15A
NM_016239.4 synonymous
NM_016239.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00600
Genes affected
MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 17-18119064-G-A is Benign according to our data. Variant chr17-18119064-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.006 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.264G>A | p.Thr88= | synonymous_variant | 2/66 | ENST00000647165.2 | NP_057323.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.264G>A | p.Thr88= | synonymous_variant | 2/66 | NM_016239.4 | ENSP00000495481 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000703 AC: 17AN: 241706Hom.: 0 AF XY: 0.0000603 AC XY: 8AN XY: 132676
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1459856Hom.: 1 Cov.: 35 AF XY: 0.0000427 AC XY: 31AN XY: 726192
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GnomAD4 genome AF: 0.0000656 AC: 10AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 27, 2016 | p.Thr88Thr in exon 2 of MYO15A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 6/58966 European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs571886925). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 13, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at