rs587776358

chr15-43618242-A-Gchr15-43618242-A-Cchr15-43618242-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: 3.27

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]

ACMG classification

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	UniProt
STRC	NM_153700.2	c.179T>C	p.Phe60Ser	missense_variant	2/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.179T>C	p.Phe60Ser	missense_variant	2/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 30410 AN: 88536 Hom.: 6287 Cov.: 11 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

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.: 7 AF XY: 0.303 AC XY: 88794 AN XY: 293154

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.: 11 AF XY: 0.340 AC XY: 13940 AN XY: 41038

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:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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, 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 ). -

Autosomal recessive nonsyndromic hearing loss 16 Benign:2 Other:1

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	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided Benign:1

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	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	17
Dann	Benign	0.54
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.000040	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.8e-8	P;P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.26
ClinPred		0.0030	T
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

Other links and lift over

dbSNP: rs2729509; hg19: chr15-43910440; COSMIC: COSV70833187; COSMIC: COSV70833187;