rs876658007
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_153700.2(STRC):c.2494C>T(p.Arg832Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000042 ( 0 hom., cov: 6)
Exomes 𝑓: 0.000045 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
STRC
NM_153700.2 missense
NM_153700.2 missense
Scores
5
9
4
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.2494C>T | p.Arg832Trp | missense_variant | 8/29 | ENST00000450892.7 | NP_714544.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.2494C>T | p.Arg832Trp | missense_variant | 8/29 | 5 | NM_153700.2 | ENSP00000401513.2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 47476Hom.: 0 Cov.: 6 FAILED QC
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GnomAD3 exomes AF: 0.0000403 AC: 2AN: 49592Hom.: 0 AF XY: 0.0000398 AC XY: 1AN XY: 25114
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000449 AC: 12AN: 267192Hom.: 0 Cov.: 4 AF XY: 0.0000413 AC XY: 6AN XY: 145166
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000421 AC: 2AN: 47476Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0AN XY: 22156
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 13, 2021 | The p.Arg832Trp variant in STRC has been identified by our laboratory in two individuals with hearing loss who also had a STRC/CATSPER2 deletion. This variant has been identified in 0.0001% (1/10124) Latino/Admixed American chromosomes and 0.006% (1/1742) other chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, these frequency estimates may not be reliable due to low coverage of this region. Computational prediction tools and conservation analyses suggest that the Arg832Trp variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM3_Strong, PP3. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2024 | Reported in a patient with bilateral sensorineural hearing loss who also harbored a gene conversion event involving the STRC gene on the opposite allele (in trans) in the published literature (PMID: 36086952); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36086952) - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2021 | The c.2494C>T (p.R832W) alteration is located in exon 8 (coding exon 8) of the STRC gene. This alteration results from a C to T substitution at nucleotide position 2494, causing the arginine (R) at amino acid position 832 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;N
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0093);.;
MVP
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