NM_153700.2:c.4863C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_153700.2(STRC):c.4863C>G(p.Leu1621Leu) 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

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 165299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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.4863C>G	p.Leu1621Leu	synonymous	Exon 26 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.4863C>G	p.Leu1621Leu	synonymous	Exon 26 of 29	ENSP00000401513.2	Q7RTU9
STRC	ENST00000440125.5	TSL:1	n.*2655C>G		non_coding_transcript_exon	Exon 25 of 28	ENSP00000394866.1	E7EPM8
STRC	ENST00000440125.5	TSL:1	n.*2655C>G		3_prime_UTR	Exon 25 of 28	ENSP00000394866.1	E7EPM8

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

GnomAD2 exomes

AF:

0.00267

AC:

669

AN:

250786

AF XY:

0.00281

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 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

African (AFR)

AF:

0.00831

AC:

276

AN:

33202

American (AMR)

AF:

0.000962

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00482

AC:

126

AN:

26132

East Asian (EAS)

AF:

0.000277

AC:

AN:

39688

South Asian (SAS)

AF:

0.0109

AC:

929

AN:

85456

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00110

AC:

1226

AN:

1111842

Other (OTH)

AF:

0.00199

AC:

120

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

117

234

352

469

586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00450

AC:

684

AN:

151948

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

328

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0107

AC:

445

AN:

41398

American (AMR)

AF:

0.00138

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0217

AC:

104

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00122

AC:

AN:

67952

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

123

154

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:

0.00120

Hom.:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.0

(source)

DANN

Benign

0.68

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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