rs12437957
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_153700.2(STRC):c.4845-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,579,662 control chromosomes in the GnomAD database, including 21,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 6081 hom., cov: 28)
Exomes 𝑓: 0.11 ( 15850 hom. )
Consequence
STRC
NM_153700.2 splice_polypyrimidine_tract, intron
NM_153700.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0730
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
Variant 15-43600695-A-G is Benign according to our data. Variant chr15-43600695-A-G is described in ClinVar as [Benign]. Clinvar id is 178635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43600695-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.4845-13T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000450892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.4845-13T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_153700.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.220 AC: 33382AN: 151506Hom.: 6068 Cov.: 28
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GnomAD3 exomes AF: 0.153 AC: 37775AN: 246558Hom.: 4789 AF XY: 0.145 AC XY: 19271AN XY: 133250
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GnomAD4 exome AF: 0.111 AC: 158193AN: 1428042Hom.: 15850 Cov.: 34 AF XY: 0.112 AC XY: 79332AN XY: 711096
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GnomAD4 genome ? AF: 0.221 AC: 33439AN: 151620Hom.: 6081 Cov.: 28 AF XY: 0.217 AC XY: 16095AN XY: 74142
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | 4845-13T>C in Intron 25 of STRC: This variant is not expected to have clinical s ignificance because it has been identified in 42.3% (1581/3738) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs12437957). - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Autosomal recessive nonsyndromic hearing loss 16 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at