rs3097773

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_153700.2(STRC):c.4842C>T(p.Phe1614=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,608,376 control chromosomes in the GnomAD database, including 35,608 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 11393 hom., cov: 27)

Exomes 𝑓: 0.13 ( 24215 hom. )

Consequence

STRC
NM_153700.2 splice_region, synonymous

Scores

Splicing: ADA: 0.2833

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.57

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-43600874-G-A is Benign according to our data. Variant chr15-43600874-G-A is described in ClinVar as [Benign]. Clinvar id is 177982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600874-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.4842C>T	p.Phe1614=	splice_region_variant, synonymous_variant	25/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.4842C>T	p.Phe1614=	splice_region_variant, synonymous_variant	25/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43416

AN:

150938

Hom.:

11362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.688

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.0980

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.195

AC:

48896

AN:

250948

Hom.:

8429

AF XY:

0.183

AC XY:

24832

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.440

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.0753

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.135

AC:

196190

AN:

1457324

Hom.:

24215

Cov.:

AF XY:

0.135

AC XY:

97757

AN XY:

725142

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0763

Gnomad4 NFE exome

AF:

0.0979

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.288

AC:

43500

AN:

151052

Hom.:

11393

Cov.:

AF XY:

0.284

AC XY:

20912

AN XY:

73714

show subpopulations

Gnomad4 AFR

AF:

0.688

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.0784

Gnomad4 NFE

AF:

0.0980

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.168

Hom.:

1521

Bravo

AF:

0.322

Asia WGS

AF:

0.350

AC:

1214

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 26, 2013	Phe1614Phe in Exon 25 of STRC: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 68% (2942/4400) of Africa n American chromosomes from a broad population by the NHBLI Exon sequencing proj ect (http://evs.gs.washington.edu/EVS/; dbSNP rs3097773). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

-0.45

Cadd

Benign

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.28

dbscSNV1_RF

Benign

0.56

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.40

Position offset: -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