rs1553776036
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_174878.3(CLRN1):c.188_210del(p.Tyr63CysfsTer59) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y63Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CLRN1
NM_174878.3 frameshift
NM_174878.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.42
Genes affected
CLRN1 (HGNC:12605): (clarin 1) This gene encodes a protein that contains a cytosolic N-terminus, multiple helical transmembrane domains, and an endoplasmic reticulum membrane retention signal, TKGH, in the C-terminus. The encoded protein may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIIa. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-150972498-CACCCTCTCCGTGGAAAAGCCCGT-C is Pathogenic according to our data. Variant chr3-150972498-CACCCTCTCCGTGGAAAAGCCCGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 4398.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-150972498-CACCCTCTCCGTGGAAAAGCCCGT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLRN1 | NM_174878.3 | c.188_210del | p.Tyr63CysfsTer59 | frameshift_variant | 1/3 | ENST00000327047.6 | |
CLRN1 | NM_001195794.1 | c.188_210del | p.Tyr63CysfsTer59 | frameshift_variant | 1/4 | ||
CLRN1 | NM_001256819.2 | c.188_210del | p.Tyr63CysfsTer19 | frameshift_variant | 1/4 | ||
CLRN1 | NR_046380.3 | n.207_229del | non_coding_transcript_exon_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLRN1 | ENST00000327047.6 | c.188_210del | p.Tyr63CysfsTer59 | frameshift_variant | 1/3 | 1 | NM_174878.3 | P1 | |
ENST00000469268.1 | n.236-29073_236-29051del | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLRN1-AS1 | ENST00000476886.5 | n.124-90425_124-90403del | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Usher syndrome type 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at