chr15-43600664-G-C

Position:

chr15-43600664-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_153700.2(STRC):c.4863C>G(p.Leu1621=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,612,422 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 28)

Exomes 𝑓: 0.0019 ( 49 hom. )

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.53

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 15-43600664-G-C is Benign according to our data. Variant chr15-43600664-G-C is described in ClinVar as [Benign]. Clinvar id is 165299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600664-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0045 (684/151948) while in subpopulation SAS AF= 0.0217 (104/4796). AF 95% confidence interval is 0.0183. There are 5 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.4863C>G	p.Leu1621=	synonymous_variant	26/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.4863C>G	p.Leu1621=	synonymous_variant	26/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes

AF:

0.00452

AC:

686

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00267

AC:

669

AN:

250786

Hom.:

AF XY:

0.00281

AC XY:

381

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00921

Gnomad AMR exome

AF:

0.000984

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00937

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00187

AC:

2737

AN:

1460474

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1558

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.00831

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00450

AC:

684

AN:

151948

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

328

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00120

Hom.:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	STRC: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 11, 2013

Leu1621Leu in Exon 26 of STRC: This variant is not expected to have clinical sig nificance because it has been observed in 0.5% (23/4410) of African American chr omosomes by the NHLBI Exome Sequencing Project, it does not alter an amino acid residue, and it is not located within the splice consensus sequence (http://evs. gs.washington.edu/EVS/; dbSNP rs139683375). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.0

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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