rs200770543

Positions:

chr15-43599999-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153700.2(STRC):c.5200T>C(p.Trp1734Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,440,188 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 21)

Exomes 𝑓: 0.0017 ( 22 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.10

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:

CKMT1B (HGNC:1995): (creatine kinase, mitochondrial 1B) Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

CKMT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014477223).

BP6

Variant 15-43599999-A-G is Benign according to our data. Variant chr15-43599999-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 505196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43599999-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.5200T>C	p.Trp1734Arg	missense_variant	28/29	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.5200T>C	p.Trp1734Arg	missense_variant	28/29	5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

171

AN:

143872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00122

Gnomad AMI

AF:

0.0145

Gnomad AMR

AF:

0.000422

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:

0.00158

Gnomad OTH

AF:

0.000517

GnomAD3 exomes

AF:

0.000955

AC:

192

AN:

201040

Hom.:

AF XY:

0.000922

AC XY:

AN XY:

107324

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000559

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00168

AC:

2424

AN:

1440188

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1200

AN XY:

716502

show subpopulations

Gnomad4 AFR exome

AF:

0.000785

Gnomad4 AMR exome

AF:

0.000456

Gnomad4 ASJ exome

AF:

0.0000774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.00212

Gnomad4 OTH exome

AF:

0.000838

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00119

AC:

171

AN:

143980

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

69778

show subpopulations

Gnomad4 AFR

AF:

0.00122

Gnomad4 AMR

AF:

0.000422

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00158

Gnomad4 OTH

AF:

0.000512

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00129

ESP6500AA

AF:

0.000914

AC:

ESP6500EA

AF:

0.00117

AC:

ExAC

AF:

0.000769

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	STRC: BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 25, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 21, 2016

p.Trp1734Arg in exon 28 of STRC: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (53/20438) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200770543). -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.23

Sift

Benign

0.055

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.10

B;B

Vest4

0.60

MutPred

0.35

Loss of helix (P = 0.0104);.;

MVP

0.66

ClinPred

0.012

GERP RS

2.4

Varity_R

0.18

gMVP

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over