rs12437957

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153700.2(STRC):c.4845-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,579,662 control chromosomes in the GnomAD database, including 21,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 6081 hom., cov: 28)

Exomes 𝑓: 0.11 ( 15850 hom. )

Consequence

STRC
NM_153700.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0730

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 15-43600695-A-G is Benign according to our data. Variant chr15-43600695-A-G is described in ClinVar as [Benign]. Clinvar id is 178635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600695-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.4845-13T>C		intron_variant	Intron 25 of 28	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 link	c.4845-13T>C		intron_variant	Intron 25 of 28	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33382

AN:

151506

Hom.:

6068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.153

AC:

37775

AN:

246558

Hom.:

4789

AF XY:

0.145

AC XY:

19271

AN XY:

133250

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0914

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.111

AC:

158193

AN:

1428042

Hom.:

15850

Cov.:

AF XY:

0.112

AC XY:

79332

AN XY:

711096

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0396

Gnomad4 NFE exome

AF:

0.0863

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.221

AC:

33439

AN:

151620

Hom.:

6081

Cov.:

AF XY:

0.217

AC XY:

16095

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.105

Hom.:

327

Bravo

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

4845-13T>C in Intron 25 of STRC: This variant is not expected to have clinical s ignificance because it has been identified in 42.3% (1581/3738) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs12437957). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

6.7

DANN

Benign

0.56

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