Genetic Variant STRC:p.Ala304Glu (chr15-43616655-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153700.2(STRC):c.911C>A(p.Ala304Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000058 ( 0 hom., cov: 10)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09164804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.911C>A	p.Ala304Glu	missense_variant	Exon 4 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STRC	ENST00000450892.7 link	c.911C>A	p.Ala304Glu	missense_variant	Exon 4 of 29	5	NM_153700.2	ENSP00000401513.2	Q7RTU9
ENSG00000284772	ENST00000643290.1 link	n.*1074C>A		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000495476.1	A0A2R8Y6Q2
ENSG00000284772	ENST00000643290.1 link	n.*1074C>A		3_prime_UTR_variant	Exon 6 of 9			ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

86488

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000688

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000561

AC:

AN:

53470

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

26980

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000964

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.0000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

AN:

429918

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

226596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000551

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000797

Gnomad4 NFE exome

AF:

0.0000891

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000578

AC:

AN:

86570

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

39406

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000121

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.0000688

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.58

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.89

N;D

REVEL

Uncertain

0.41

Sift

Benign

0.036

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.028

B;.

Vest4

0.60

MutPred

0.31

Gain of solvent accessibility (P = 0.0411);.;

MVP

0.73

ClinPred

0.092

GERP RS

4.0

Varity_R

0.23

gMVP

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over