15-43600596-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153700.2(STRC):​c.4931G>A​(p.Gly1644Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)

Consequence

STRC
NM_153700.2 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STRCNM_153700.2 linkc.4931G>A p.Gly1644Asp missense_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.4931G>A p.Gly1644Asp missense_variant Exon 26 of 29 5 NM_153700.2 ENSP00000401513.2 Q7RTU9

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
26
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4931G>A (p.G1644D) alteration is located in exon 26 (coding exon 26) of the STRC gene. This alteration results from a G to A substitution at nucleotide position 4931, causing the glycine (G) at amino acid position 1644 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.81
T;T
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Benign
-0.38
T
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.93
N;N
REVEL
Uncertain
0.33
Sift
Benign
0.21
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.90
P;B
Vest4
0.63
MutPred
0.41
Gain of solvent accessibility (P = 0.0638);.;
MVP
0.77
ClinPred
0.57
D
GERP RS
3.8
Varity_R
0.13
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2085657484; hg19: chr15-43892794; API