rs1360568237

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153700.2(STRC):c.995C>G(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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.854

Publications

0 publications found

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]

STRC Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 16
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

STRC links:

ENSG00000284772 (HGNC:):

ENSG00000284772 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.995C>G	p.Ser332Cys	missense_variant	Exon 4 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STRC	ENST00000450892.7 link	c.995C>G	p.Ser332Cys	missense_variant	Exon 4 of 29	5	NM_153700.2	ENSP00000401513.2	Q7RTU9
ENSG00000284772	ENST00000643290.1 link	n.*1158C>G		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000495476.1	A0A2R8Y6Q2
ENSG00000284772	ENST00000643290.1 link	n.*1158C>G		3_prime_UTR_variant	Exon 6 of 9			ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes

AF:

0.0000402

AC:

AN:

24868

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000748

AC:

AN:

53496

AF XY:

0.0000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000783

AC:

AN:

421528

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

221906

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

11638

American (AMR)

AF:

0.00

AC:

AN:

17834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13078

East Asian (EAS)

AF:

0.00

AC:

AN:

28860

South Asian (SAS)

AF:

0.000682

AC:

AN:

43974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26726

Middle Eastern (MID)

AF:

0.000541

AC:

AN:

1850

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

253132

Other (OTH)

AF:

0.0000818

AC:

AN:

24436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.314

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000403

AC:

AN:

24836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

10658

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

4946

American (AMR)

AF:

0.00

AC:

AN:

2626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

676

East Asian (EAS)

AF:

0.00

AC:

AN:

1562

South Asian (SAS)

AF:

0.000843

AC:

AN:

1186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

11904

Other (OTH)

AF:

0.00

AC:

AN:

402

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The 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

Apr 12, 2022

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.78

PhyloP100

0.85

PrimateAI

Uncertain

0.53

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

GERP RS

1.7

Varity_R

0.093

gMVP

0.45

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1360568237

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over