15-43611493-ACTCACATCGTGCCTAG-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePP5_Moderate
The NM_153700.2(STRC):c.3128_3138+5del variant causes a splice donor, splice donor 5th base, coding sequence, intron change. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 4)
Consequence
STRC
NM_153700.2 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_153700.2 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.007132132 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP5
Variant 15-43611493-ACTCACATCGTGCCTAG-A is Pathogenic according to our data. Variant chr15-43611493-ACTCACATCGTGCCTAG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 505025.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.3128_3138+5del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 12/29 | ENST00000450892.7 | NP_714544.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.3128_3138+5del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 12/29 | 5 | NM_153700.2 | ENSP00000401513 | P2 |
Frequencies
GnomAD3 genomes Cov.: 4
GnomAD3 genomes
Cov.:
4
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 4
GnomAD4 genome
Cov.:
4
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 02, 2016 | The c.3128_3138+5del variant in STRC has been reported in one individual with he aring loss (Mandelker 2014, LMM data). Data from large population studies are i nsufficient to assess the frequency of this variant. This variant is a deletion of 16 nucleotides encompassing 11 nucleotides of exon 12 and 5 nucleotides of in tron 12, which includes the invariant region (+/- 1/2) of the splice consensus s equence. This deletion is predicted to cause altered splicing leading to an abno rmal or absent protein. Loss-of-function variants in the STRC gene are causative for autosomal recessive hearing loss. In summary, although additional studies a re required to fully establish its clinical significance, this variant is likely pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at