chr15-43600227-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_153700.2(STRC):c.5060C>A(p.Ala1687Asp) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09

Publications

1 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: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

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.5060C>A	p.Ala1687Asp	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.5060C>A	p.Ala1687Asp	missense	Exon 27 of 29	ENSP00000401513.2	Q7RTU9
STRC	ENST00000440125.5	TSL:1	n.*2852C>A		non_coding_transcript_exon	Exon 26 of 28	ENSP00000394866.1	E7EPM8
STRC	ENST00000440125.5	TSL:1	n.*2852C>A		3_prime_UTR	Exon 26 of 28	ENSP00000394866.1	E7EPM8

Frequencies

GnomAD3 genomes

AF:

0.0000277

AC:

AN:

144660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000515

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:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

145468

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1187704

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

595412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27816

American (AMR)

AF:

0.00

AC:

AN:

36094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23796

East Asian (EAS)

AF:

0.00

AC:

AN:

35566

South Asian (SAS)

AF:

0.00

AC:

AN:

75334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5038

European-Non Finnish (NFE)

AF:

0.0000238

AC:

AN:

884068

Other (OTH)

AF:

0.00

AC:

AN:

51198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.0000277

AC:

AN:

144660

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

70046

show subpopulations

African (AFR)

AF:

0.0000515

AC:

AN:

38844

American (AMR)

AF:

0.00

AC:

AN:

14176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

4780

South Asian (SAS)

AF:

0.00

AC:

AN:

4310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66090

Other (OTH)

AF:

0.00

AC:

AN:

1900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive nonsyndromic hearing loss 16 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.078

PhyloP100

7.1

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.75

MutPred

0.52

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.89

ClinPred

1.0

GERP RS

4.8

Varity_R

0.61

gMVP

0.89

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over