rs749407115
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate
The NM_153700.2(STRC):c.4844+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
STRC
NM_153700.2 intron
NM_153700.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0440
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 15-43600857-C-T is Benign according to our data. Variant chr15-43600857-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227971.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.4844+15G>A | intron_variant | ENST00000450892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.4844+15G>A | intron_variant | 5 | NM_153700.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151856Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251274Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135862
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461684Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 727144
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151974Hom.: 0 Cov.: 28 AF XY: 0.0000269 AC XY: 2AN XY: 74252
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 10, 2015 | c.4844+15G>A in intron 25 of STRC: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 0.1% (6/8648) of East Asian chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org). - |
Computational scores
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BayesDel_noAF
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -21
Find out detailed SpliceAI scores and Pangolin per-transcript scores at