rs757152351
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_153700.2(STRC):c.436G>A(p.Gly146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 19)
Exomes 𝑓: 0.000017 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
STRC
NM_153700.2 missense
NM_153700.2 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 2.23
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 Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3202406).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.436G>A | p.Gly146Arg | missense_variant | 2/29 | ENST00000450892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.436G>A | p.Gly146Arg | missense_variant | 2/29 | 5 | NM_153700.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152268Hom.: 0 Cov.: 19 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000171 AC: 25AN: 1461642Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727132
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0AN XY: 74398
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2015 | The p.Gly146Arg variant in STRC has not been previously reported in individuals with hearing loss. Data from large population studies are insufficient to asses s the frequency of this variant. Computational prediction tools and conservatio n analyses do not provide strong support for or against an impact to the protein . In summary, the clinical significance of the Gly146Arg variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0306);.;
MVP
ClinPred
D
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