rs1360568237

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153700.2(STRC):ā€‹c.995C>Gā€‹(p.Ser332Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.000040 ( 0 hom., cov: 4)
Exomes š‘“: 0.000078 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.854
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1498234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STRCNM_153700.2 linkuse as main transcriptc.995C>G p.Ser332Cys missense_variant 4/29 ENST00000450892.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STRCENST00000450892.7 linkuse as main transcriptc.995C>G p.Ser332Cys missense_variant 4/295 NM_153700.2 P2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
24868
Hom.:
0
Cov.:
4
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000825
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000783
AC:
33
AN:
421528
Hom.:
0
Cov.:
0
AF XY:
0.000113
AC XY:
25
AN XY:
221906
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000682
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000818
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000403
AC:
1
AN:
24836
Hom.:
0
Cov.:
4
AF XY:
0.00
AC XY:
0
AN XY:
10658
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000843
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineDec 14, 2017The p.Ser332Cys variant in STRC has not been previously reported in individuals with hearing loss. It has been reported in 4/49214 chromosomes the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org). Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser332 Cys variant is uncertain. ACMG/AMP Criteria applied: None. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMayo Clinic Laboratories, Mayo ClinicApr 12, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.033
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.049
T;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.62
N;D
REVEL
Benign
0.21
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.019
D;D
Polyphen
0.80
P;.
Vest4
0.18
MutPred
0.14
Loss of relative solvent accessibility (P = 0.0186);.;
MVP
0.73
ClinPred
0.039
T
GERP RS
1.7
Varity_R
0.093
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1360568237; hg19: chr15-43908769; API