rs56385906

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_153700.2(STRC):c.3360T>C(p.Cys1120Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 146,078 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 86 hom., cov: 22)

Exomes 𝑓: 0.011 ( 2718 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.191

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-43610931-A-G is Benign according to our data. Variant chr15-43610931-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 227082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43610931-A-G is described in Lovd as [Benign]. Variant chr15-43610931-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.191 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2784/146078) while in subpopulation NFE AF= 0.031 (1996/64330). AF 95% confidence interval is 0.0299. There are 86 homozygotes in gnomad4. There are 1325 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.3360T>C	p.Cys1120Cys	synonymous_variant	Exon 14 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.3360T>C	p.Cys1120Cys	synonymous_variant	Exon 14 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2787

AN:

145958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00382

Gnomad AMI

AF:

0.0215

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0183

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0133

AC:

3179

AN:

238230

Hom.:

326

AF XY:

0.0132

AC XY:

1690

AN XY:

128488

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.00877

Gnomad FIN exome

AF:

0.00754

Gnomad NFE exome

AF:

0.0186

Gnomad OTH exome

AF:

0.0193

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0111

AC:

15335

AN:

1381298

Hom.:

2718

Cov.:

AF XY:

0.0112

AC XY:

7682

AN XY:

688280

show subpopulations

Gnomad4 AFR exome

AF:

0.000906

Gnomad4 AMR exome

AF:

0.00891

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00681

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.0191

AC:

2784

AN:

146078

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1325

AN XY:

71594

show subpopulations

Gnomad4 AFR

AF:

0.00379

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.0183

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0387

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 05, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 26, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cys1120Cys in Exon 14 of STRC: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 7.6% (10/132) of chromoso mes from an European American (CEU) population in 1000Genomes project (reported in Deafness Variation Database: http://deafnessvariationdatabase.org; dbSNP rs56 385906). -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.8

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over