NM_153700.2:c.4561C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153700.2(STRC):c.4561C>T(p.Arg1521Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,611,700 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1521Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0050 ( 18 hom., cov: 29)

Exomes 𝑓: 0.0034 ( 97 hom. )

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.518

Publications

5 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073873997).

BP6

Variant 15-43601536-G-A is Benign according to our data. Variant chr15-43601536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.4561C>T	p.Arg1521Trp	missense_variant	Exon 24 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.4561C>T	p.Arg1521Trp	missense_variant	Exon 24 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.00504

AC:

766

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00491

AC:

1234

AN:

251096

AF XY:

0.00488

show subpopulations

Gnomad AFR exome

AF:

0.00253

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00337

AC:

4919

AN:

1459668

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2467

AN XY:

726172

show subpopulations

African (AFR)

AF:

0.00320

AC:

107

AN:

33462

American (AMR)

AF:

0.000738

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26104

East Asian (EAS)

AF:

0.000101

AC:

AN:

39674

South Asian (SAS)

AF:

0.000394

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.0358

AC:

1909

AN:

53372

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00237

AC:

2630

AN:

1110052

Other (OTH)

AF:

0.00302

AC:

182

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

272

544

817

1089

1361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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

AF:

0.00503

AC:

765

AN:

152032

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

486

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00268

AC:

111

AN:

41466

American (AMR)

AF:

0.000721

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0393

AC:

416

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00316

AC:

215

AN:

67946

Other (OTH)

AF:

0.00380

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00253

Hom.:

Bravo

AF:

0.00213

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00451

AC:

547

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00241

EpiControl

AF:

0.00244

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 03, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Arg1521Trp in exon 24 of STRC: This variant is not expected to have clinical s ignificance because it has been identified in 3.9% (254/6588) of Finnish chromos omes including 8 homozygotes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs138763871), and the arginine (Arg) residue at po sition 1521 is not conserved through species. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.63

PhyloP100

0.52

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;D

Vest4

0.52

MVP

0.84

ClinPred

0.020

GERP RS

0.40

Varity_R

0.095

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over