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NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter) AND Nonsyndromic genetic hearing loss

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 28, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002240823.1

Allele description [Variation Report for NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter)]

NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter)

Gene:
MYO15A:myosin XVA [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter)
Other names:
NM_016239.4(MYO15A):c.10045C>T; p.Gln3349Ter
HGVS:
  • NC_000017.11:g.18167686C>T
  • NG_011634.2:g.63981C>T
  • NM_016239.4:c.10045C>TMANE SELECT
  • NP_057323.3:p.Gln3349Ter
  • NC_000017.10:g.18071000C>T
  • NG_011634.1:g.63981C>T
  • NM_016239.3:c.10045C>T
Protein change:
Q3349*
Links:
dbSNP: rs1345580310
NCBI 1000 Genomes Browser:
rs1345580310
Molecular consequence:
  • NM_016239.4:c.10045C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Nonsyndromic genetic hearing loss
Synonyms:
Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:
MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002512117ClinGen Hearing Loss Variant Curation Expert Panel
reviewed by expert panel

(clingen hl acmg specifications otof myo15a v1)		Pathogenic
(Sep 28, 2021) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV002512117.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The allele frequency of the c.10045C>T (p.Gln3349Ter) variant in the MYO15A gene is 0.002% (2/112392) of European non-Finnish alleles by gnomAD v2.1.1, which is a low enough frequency to apply PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_Supporting). This variant has been detected in 1 patient with hearing loss in trans with a pathogenic variant (PM3_Supporting, Partners LMM internal data SCV001365783.1). The p.Gln3349Ter variant in MYO15A is predicted to cause a premature stop codon in biologically-relevant-exon 62/66 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting, PM3_Supporting, PVS1.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023