chr15-43618242-A-G

Position:

chr15-43618242-A-G

Variant summary

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

The NM_153700.2(STRC):c.179T>C(p.Phe60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 6309 hom., cov: 11)

Exomes 𝑓: 0.30 ( 26224 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 3.27

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:

ENSG00000284772 (HGNC:):

ENSG00000284772 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=3.956515E-5).

BP6

Variant 15-43618242-A-G is Benign according to our data. Variant chr15-43618242-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 156030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43618242-A-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.179T>C	p.Phe60Ser	missense_variant	2/29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.179T>C	p.Phe60Ser	missense_variant	2/29	5	NM_153700.2	ENSP00000401513.2	Q7RTU9
ENSG00000284772	ENST00000643290.1 linkuse as main transcript	n.*342T>C		non_coding_transcript_exon_variant	4/9			ENSP00000495476.1	A0A2R8Y6Q2
ENSG00000284772	ENST00000643290.1 linkuse as main transcript	n.*342T>C		3_prime_UTR_variant	4/9			ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

30410

AN:

88536

Hom.:

6287

Cov.:

FAILED QC

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.428

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.345

AC:

23061

AN:

66768

Hom.:

4176

AF XY:

0.341

AC XY:

11655

AN XY:

34204

show subpopulations

Gnomad AFR exome

AF:

0.680

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.301

AC:

167071

AN:

555480

Hom.:

26224

Cov.:

AF XY:

0.303

AC XY:

88794

AN XY:

293154

show subpopulations

Gnomad4 AFR exome

AF:

0.672

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.344

AC:

30462

AN:

88600

Hom.:

6309

Cov.:

AF XY:

0.340

AC XY:

13940

AN XY:

41038

show subpopulations

Gnomad4 AFR

AF:

0.638

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.259

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.187

Hom.:

456

ExAC

AF:

0.197

AC:

2282

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 26, 2013	Phe60Ser in exon 02 of STRC: This variant is not expected to have clinical signi ficance because it has been identified in ~25% of chromosomes from several popu lations by the 1000Genomes project (reported by the Deafness Variation Database: http://deafnessvariationdatabase.org; dbSNP rs143613180 ). -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 17, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
not provided, no classification provided	literature only	Genomic Research Center, Shahid Beheshti University of Medical Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 26969326) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.19

MetaRNN

Benign

0.000040

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.6

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.26

ClinPred

0.0030

GERP RS

3.4

Varity_R

0.043

gMVP

0.21

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