rs143345370
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_153700.2(STRC):āc.4035G>Cā(p.Leu1345=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,584 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.017 ( 98 hom., cov: 31)
Exomes š: 0.0017 ( 103 hom. )
Consequence
STRC
NM_153700.2 synonymous
NM_153700.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0160
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 15-43604742-C-G is Benign according to our data. Variant chr15-43604742-C-G is described in ClinVar as [Benign]. Clinvar id is 165307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.016 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.4035G>C | p.Leu1345= | synonymous_variant | 20/29 | ENST00000450892.7 | NP_714544.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.4035G>C | p.Leu1345= | synonymous_variant | 20/29 | 5 | NM_153700.2 | ENSP00000401513 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0170 AC: 2582AN: 151974Hom.: 86 Cov.: 31
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GnomAD3 exomes AF: 0.00450 AC: 1129AN: 251014Hom.: 42 AF XY: 0.00335 AC XY: 455AN XY: 135682
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GnomAD4 exome AF: 0.00165 AC: 2417AN: 1461492Hom.: 103 Cov.: 33 AF XY: 0.00142 AC XY: 1036AN XY: 727060
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GnomAD4 genome AF: 0.0173 AC: 2624AN: 152092Hom.: 98 Cov.: 31 AF XY: 0.0171 AC XY: 1268AN XY: 74350
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Leu1345Leu in Exon 20 of STRC: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 5.8% (215/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs143345370). - |
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