15-43600682-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153700.2(STRC):​c.4845C>G​(p.Ser1615Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 28)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

STRC
NM_153700.2 missense, splice_region

Scores

3
7
8
Splicing: ADA: 0.003945
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STRCNM_153700.2 linkc.4845C>G p.Ser1615Arg missense_variant, splice_region_variant Exon 26 of 29 ENST00000450892.7 NP_714544.1 Q7RTU9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STRCENST00000450892.7 linkc.4845C>G p.Ser1615Arg missense_variant, splice_region_variant Exon 26 of 29 5 NM_153700.2 ENSP00000401513.2 Q7RTU9

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461434
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.042
T;.
Eigen
Benign
-0.063
Eigen_PC
Benign
-0.084
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.81
T;T
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Benign
-0.30
T
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.77
N;N
REVEL
Uncertain
0.50
Sift
Benign
0.22
T;T
Sift4G
Uncertain
0.024
D;D
Polyphen
1.0
D;P
Vest4
0.73
MutPred
0.55
Gain of catalytic residue at S1615 (P = 0.0103);.;
MVP
0.76
ClinPred
0.65
D
GERP RS
1.8
Varity_R
0.078
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0039
dbscSNV1_RF
Benign
0.15
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-43892880; API