rs712270
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_016239.4(MYO15A):c.8045A>T(p.Tyr2682Phe) variant causes a missense change. The variant allele was found at a frequency of 0.384 in 1,613,226 control chromosomes in the GnomAD database, including 124,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.34 ( 9358 hom., cov: 32)
Exomes 𝑓: 0.39 ( 115617 hom. )
Consequence
MYO15A
NM_016239.4 missense
NM_016239.4 missense
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 6.34
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0023952425).
BP6
?
Variant 17-18153853-A-T is Benign according to our data. Variant chr17-18153853-A-T is described in ClinVar as [Benign]. Clinvar id is 226790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18153853-A-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.8045A>T | p.Tyr2682Phe | missense_variant | 43/66 | ENST00000647165.2 | |
LOC105371567 | XR_001752809.1 | n.329T>A | non_coding_transcript_exon_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.8045A>T | p.Tyr2682Phe | missense_variant | 43/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.336 AC: 51019AN: 151856Hom.: 9356 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.336 AC: 83706AN: 248882Hom.: 15506 AF XY: 0.336 AC XY: 45427AN XY: 135276
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GnomAD4 exome AF: 0.389 AC: 568319AN: 1461252Hom.: 115617 Cov.: 53 AF XY: 0.384 AC XY: 278872AN XY: 726932
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GnomAD4 genome ? AF: 0.336 AC: 51031AN: 151974Hom.: 9358 Cov.: 32 AF XY: 0.330 AC XY: 24513AN XY: 74320
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1675
ESP6500AA
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Tyr2682Phe in Exon 43 of MYO15A: This variant is not expected to have clinical s ignificance because it has been identified in 39.8% (2646/6644) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs712270). - |
Autosomal recessive nonsyndromic hearing loss 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;.
Polyphen
1.0
.;D;D
Vest4
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at