rs754612418

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153700.2(STRC):c.5047G>A(p.Val1683Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000057 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05244264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.5047G>A	p.Val1683Ile	missense	Exon 27 of 29	NP_714544.1	Q7RTU9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STRC	ENST00000450892.7	TSL:5 MANE Select	c.5047G>A	p.Val1683Ile	missense	Exon 27 of 29	ENSP00000401513.2	Q7RTU9
STRC	ENST00000440125.5	TSL:1	n.*2839G>A		non_coding_transcript_exon	Exon 26 of 28	ENSP00000394866.1	E7EPM8
STRC	ENST00000440125.5	TSL:1	n.*2839G>A		3_prime_UTR	Exon 26 of 28	ENSP00000394866.1	E7EPM8

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

145594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000604

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000696

AC:

AN:

143648

AF XY:

0.0000910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000728

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000572

AC:

AN:

1135780

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

570516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26752

American (AMR)

AF:

0.000225

AC:

AN:

35612

Ashkenazi Jewish (ASJ)

AF:

0.0000426

AC:

AN:

23466

East Asian (EAS)

AF:

0.00

AC:

AN:

34836

South Asian (SAS)

AF:

0.0000270

AC:

AN:

73972

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4576

European-Non Finnish (NFE)

AF:

0.0000620

AC:

AN:

839006

Other (OTH)

AF:

0.0000202

AC:

AN:

49426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000275

AC:

AN:

145594

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39192

American (AMR)

AF:

0.00

AC:

AN:

14368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

4826

South Asian (SAS)

AF:

0.00

AC:

AN:

4352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000604

AC:

AN:

66266

Other (OTH)

AF:

0.00

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000106

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.018

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.32

M_CAP

Benign

0.029

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.98

PhyloP100

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

0.65

REVEL

Benign

0.087

Sift

Benign

0.38

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.12

MutPred

0.35

Gain of catalytic residue at P1685 (P = 0.0393)

MVP

0.47

ClinPred

0.019

GERP RS

3.0

Varity_R

0.027

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over