Variant chr15-43617727-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_153700.2(STRC):c.694A>G(p.Lys232Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000078 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059924692).

BP6

Variant 15-43617727-T-C is Benign according to our data. Variant chr15-43617727-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.694A>G	p.Lys232Glu	missense_variant	2/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.694A>G	p.Lys232Glu	missense_variant	2/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

128080

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000759

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000103

AC:

AN:

1169060

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

587074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000807

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000575

Gnomad4 OTH exome

AF:

0.0000796

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000780

AC:

AN:

128186

Hom.:

Cov.:

AF XY:

0.0000162

AC XY:

AN XY:

61792

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Dec 01, 2015

p.Lys232Glu in exon 2 of STRC: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, >20 mammals have a Glutamic acid (Glu) at this position. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.1

DANN

Benign

0.66

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.67

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.12

MutPred

0.18

Loss of ubiquitination at K232 (P = 0.0067);.;

MVP

0.43

ClinPred

0.060

GERP RS

3.0

Varity_R

0.054

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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