Variant chr15-43616676-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_153700.2(STRC):c.890A>G(p.Asn297Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000077 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity STRC_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.2339066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.890A>G	p.Asn297Ser	missense_variant	4/29	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.890A>G	p.Asn297Ser	missense_variant	4/29	5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98942

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00140

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000828

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000770

AC:

AN:

415526

Hom.:

Cov.:

AF XY:

0.0000730

AC XY:

AN XY:

219132

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.000113

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:

0.00

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000323

AC:

AN:

99048

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

45892

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00

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:

0.000814

Alfa

AF:

0.000590

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 01, 2015

The p.Asn297Ser variant in STRC has not been previously reported in individuals with hearing loss. Data from large population studies is insufficient to assess the frequency of this variant. Computational prediction tools and conservation a nalysis suggest that this variant may impact the protein, though this informatio n is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Asn297Ser variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

-0.078

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.88

N;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.92

P;.

Vest4

0.56

MutPred

0.20

Gain of disorder (P = 0.0967);.;

MVP

0.87

ClinPred

0.055

GERP RS

3.8

Varity_R

0.22

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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