15-43600008-C-T

Variant summary

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

The NM_153700.2(STRC):​c.5191G>A​(p.Ala1731Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,602,480 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 21)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

STRC
NM_153700.2 missense

Scores

2
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13
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.5191G>A p.Ala1731Thr missense_variant Exon 28 of 29 ENST00000450892.7 NP_714544.1 Q7RTU9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STRCENST00000450892.7 linkc.5191G>A p.Ala1731Thr missense_variant Exon 28 of 29 5 NM_153700.2 ENSP00000401513.2 Q7RTU9

Frequencies

GnomAD3 genomes
AF:
0.00000682
AC:
1
AN:
146732
Hom.:
0
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000225
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000504
AC:
12
AN:
238030
Hom.:
0
AF XY:
0.0000622
AC XY:
8
AN XY:
128636
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000413
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000279
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000227
AC:
33
AN:
1455748
Hom.:
0
Cov.:
31
AF XY:
0.0000304
AC XY:
22
AN XY:
723944
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000462
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000223
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000682
AC:
1
AN:
146732
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
71224
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000225
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000660
AC:
8

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jun 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5191G>A (p.A1731T) alteration is located in exon 28 (coding exon 28) of the STRC gene. This alteration results from a G to A substitution at nucleotide position 5191, causing the alanine (A) at amino acid position 1731 to be replaced by a threonine (T). 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
Uncertain
0.43
BayesDel_addAF
Benign
-0.0080
T
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.33
T;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Uncertain
0.34
D
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-2.0
N;N
REVEL
Uncertain
0.46
Sift
Uncertain
0.0030
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.67
MutPred
0.24
Gain of phosphorylation at A1731 (P = 0.0304);.;
MVP
0.82
ClinPred
0.38
T
GERP RS
4.8
Varity_R
0.26
gMVP
0.66

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: rs201899170; hg19: chr15-43892206; API