rs2860666

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_153700.2(STRC):c.4917A>C(p.Leu1639Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 151,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0019 ( 29 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0820

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 15-43600610-T-G is Benign according to our data. Variant chr15-43600610-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 805531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600610-T-G is described in Lovd as [Likely_pathogenic].

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.4917A>C	p.Leu1639Leu	synonymous_variant	Exon 26 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 link	c.4917A>C	p.Leu1639Leu	synonymous_variant	Exon 26 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

265

AN:

151156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000558

Gnomad AMI

AF:

0.00225

Gnomad AMR

AF:

0.00191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00343

Gnomad FIN

AF:

0.0000949

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00118

AC:

297

AN:

251056

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00185

AC:

2696

AN:

1454202

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1304

AN XY:

722832

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000725

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

AF:

0.00175

AC:

264

AN:

151276

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

112

AN XY:

73938

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00321

Gnomad4 FIN

AF:

0.0000949

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00167

Hom.:

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STRC: BP4, BP7 -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 16;C1970187:Deafness-infertility syndrome;C2751811:Spermatogenic failure 7

Benign:1

Mar 28, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely 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

-0.56

CADD

Benign

4.9

DANN

Benign

0.66

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