Variant rs786200883 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 15 ACMG points: 16P and 1B. PVS1PP5_Very_StrongBS2_Supporting

The NM_153700.2(STRC):c.2171_2174del(p.Val724GlyfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000786 in 636,356 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000096 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000077 ( 3 hom. )

Consequence

STRC
NM_153700.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:3

Conservation

PhyloP100: 4.24

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 Pathogenic. Variant got 15 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 15-43614435-CCAAA-C is Pathogenic according to our data. Variant chr15-43614435-CCAAA-C is described in ClinVar as [Pathogenic]. Clinvar id is 4344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.2171_2174del	p.Val724GlyfsTer6	frameshift_variant	5/29	ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
STRC	ENST00000450892.7 linkuse as main transcript	c.2171_2174del	p.Val724GlyfsTer6	frameshift_variant	5/29	5	NM_153700.2	ENSP00000401513	P2
STRC	ENST00000440125.5 linkuse as main transcript	c.173_176del		3_prime_UTR_variant, NMD_transcript_variant	6/28	1		ENSP00000394866
STRC	ENST00000541030.5 linkuse as main transcript	c.62_65del	p.Val21GlyfsTer6	frameshift_variant	5/27	5		ENSP00000440413	A2
STRC	ENST00000428650.5 linkuse as main transcript	c.2171_2174del	p.Val724GlyfsTer6	frameshift_variant, NMD_transcript_variant	5/28	5		ENSP00000415991

Frequencies

GnomAD3 genomes

AF:

0.0000962

AC:

AN:

62394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

102490

Hom.:

AF XY:

0.0000362

AC XY:

AN XY:

55310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.0000237

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000767

AC:

AN:

573962

Hom.:

AF XY:

0.0000758

AC XY:

AN XY:

303608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000185

Gnomad4 NFE exome

AF:

0.0000902

Gnomad4 OTH exome

AF:

0.000112

GnomAD4 genome

AF:

0.0000962

AC:

AN:

62394

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

29628

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 16

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	The Shared Resource Centre "Genome", Research Centre for Medical Genetics	Nov 10, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 2001	- -

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

Jun 29, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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