15-43600649-G-C

Position:

chr15-43600649-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153700.2(STRC):c.4878C>G(p.Leu1626=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,611,690 control chromosomes in the GnomAD database, including 22,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 6089 hom., cov: 28)

Exomes 𝑓: 0.12 ( 16274 hom. )

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.02

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 15-43600649-G-C is Benign according to our data. Variant chr15-43600649-G-C is described in ClinVar as [Benign]. Clinvar id is 178634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600649-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.4878C>G	p.Leu1626=	synonymous_variant	26/29	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.4878C>G	p.Leu1626=	synonymous_variant	26/29	5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33399

AN:

151554

Hom.:

6075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0937

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.160

AC:

40118

AN:

250578

Hom.:

5021

AF XY:

0.152

AC XY:

20564

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.0387

Gnomad NFE exome

AF:

0.0964

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.120

AC:

174889

AN:

1460020

Hom.:

16274

Cov.:

AF XY:

0.120

AC XY:

87310

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0956

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.221

AC:

33458

AN:

151670

Hom.:

6089

Cov.:

AF XY:

0.217

AC XY:

16107

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0937

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.164

Hom.:

645

Bravo

AF:

0.248

EpiCase

AF:

0.107

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 28, 2013	Leu1626Leu in Exon 26 of STRC: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 46.0% (1721/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12438025). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.3

DANN

Benign

0.77

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