15-43611236-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153700.2(STRC):c.3218G>A(p.Arg1073Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 15)

Exomes 𝑓: 0.00068 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 1.03

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:

ENSG00000309475 (HGNC:):

ENSG00000309475 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008996576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.3218G>A	p.Arg1073Gln	missense_variant	Exon 13 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 link	c.3218G>A	p.Arg1073Gln	missense_variant	Exon 13 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.000435

AC:

AN:

121748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000172

Gnomad ASJ

AF:

0.00287

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.000689

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000854

AC:

AN:

97148

AF XY:

0.000848

show subpopulations

Gnomad AFR exome

AF:

0.000320

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.00222

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000676

AC:

495

AN:

732056

Hom.:

Cov.:

AF XY:

0.000701

AC XY:

265

AN XY:

378236

show subpopulations

African (AFR)

AF:

0.000324

AC:

AN:

21574

American (AMR)

AF:

0.00120

AC:

AN:

33218

Ashkenazi Jewish (ASJ)

AF:

0.00216

AC:

AN:

18964

East Asian (EAS)

AF:

0.0000305

AC:

AN:

32766

South Asian (SAS)

AF:

0.000370

AC:

AN:

62100

European-Finnish (FIN)

AF:

0.0000615

AC:

AN:

32530

Middle Eastern (MID)

AF:

0.00695

AC:

AN:

2732

European-Non Finnish (NFE)

AF:

0.000673

AC:

331

AN:

491954

Other (OTH)

AF:

0.000856

AC:

AN:

36218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

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:

0.000427

AC:

AN:

121864

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

AN XY:

57840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35010

American (AMR)

AF:

0.000172

AC:

AN:

11646

Ashkenazi Jewish (ASJ)

AF:

0.00287

AC:

AN:

2792

East Asian (EAS)

AF:

0.00

AC:

AN:

4098

South Asian (SAS)

AF:

0.00

AC:

AN:

3118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7496

Middle Eastern (MID)

AF:

0.0155

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.000689

AC:

AN:

55184

Other (OTH)

AF:

0.00

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00103

Hom.:

ExAC

AF:

0.000269

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Oct 28, 2022

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BS1_supporting, BP4, PM3 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2025

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis suggests that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32860223) -

Autosomal recessive nonsyndromic hearing loss 16

Uncertain:2

Feb 05, 2020

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Genome-Nilou Lab

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

Nov 25, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant classified as Uncertain Significance - Favor Benign. The p.Arg1073Gln va riant in STRC has been previously reported in three individuals with hearing los s (LMM unpublished data), one of whom had a pathogenic variant and the p.Cys1092 Tyr variant of uncertain significance in STRC; however, the cis/trans configurat ion of the variants was not determined. A second STRC variant was not detected i n the other two individuals (LMM unpublished data). This variant has been identi fied in 0.5% (4/888) of European chromosomes and in 0.4% (2/492) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs727503449); however, this allele frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation anal yses suggest that the variant may not impact the protein, though this informatio n is not predictive enough to rule out pathogenicity. In summary, while the clin ical significance of the p.Arg1073Gln variant is uncertain, the population frequ ency data suggests that it is more likely to be benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.86

PhyloP100

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.060

REVEL

Benign

0.12

Sift

Benign

0.22

Sift4G

Benign

0.088

Polyphen

0.61

Vest4

0.12

MutPred

0.34

Gain of catalytic residue at R1073 (P = 0.0753);

MVP

0.47

ClinPred

0.0059

GERP RS

3.2

Varity_R

0.068

gMVP

0.27

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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15-43611236-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over