rs56042996

Positions:

chr15-43605301-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153700.2(STRC):c.3893A>G(p.His1298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,590,212 control chromosomes in the GnomAD database, including 21,538 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5826 hom., cov: 30)

Exomes 𝑓: 0.12 ( 15712 hom. )

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.35

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021159947).

BP6

Variant 15-43605301-T-C is Benign according to our data. Variant chr15-43605301-T-C is described in ClinVar as [Benign]. Clinvar id is 165312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43605301-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.3893A>G	p.His1298Arg	missense_variant	19/29	ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.3893A>G	p.His1298Arg	missense_variant	19/29	5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32808

AN:

151178

Hom.:

5814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.0941

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.161

AC:

32392

AN:

200968

Hom.:

3859

AF XY:

0.154

AC XY:

16693

AN XY:

108198

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.0391

Gnomad NFE exome

AF:

0.0978

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.120

AC:

172233

AN:

1438918

Hom.:

15712

Cov.:

AF XY:

0.120

AC XY:

85682

AN XY:

713602

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.0401

Gnomad4 NFE exome

AF:

0.0963

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.217

AC:

32866

AN:

151294

Hom.:

5826

Cov.:

AF XY:

0.214

AC XY:

15799

AN XY:

73916

show subpopulations

Gnomad4 AFR

AF:

0.477

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.0402

Gnomad4 NFE

AF:

0.0940

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.162

Hom.:

623

Bravo

AF:

0.245

ESP6500AA

AF:

0.451

AC:

1981

ESP6500EA

AF:

0.0978

AC:

836

ExAC

AF:

0.147

AC:

17652

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	His1298Arg in Exon 19 of STRC: This variant is not expected to have clinical sig nificance because it has been identified in 44.6% (1663/3728) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs2920780). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

8.2e-8

P;P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.098

Sift

Benign

0.22

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;B

Vest4

0.13

ClinPred

0.0040

GERP RS

2.9

Varity_R

0.054

gMVP

0.39

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.

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