3-150928173-CAAT-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4_SupportingPP5_Moderate
The ENST00000327047.6(CLRN1):c.459_461del(p.Ile153_Leu154delinsMet) variant causes a inframe deletion 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CLRN1
ENST00000327047.6 inframe_deletion
ENST00000327047.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.17
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 Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in ENST00000327047.6
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000327047.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 3-150928173-CAAT-C is Pathogenic according to our data. Variant chr3-150928173-CAAT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4394.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-150928173-CAAT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLRN1 | NM_174878.3 | c.459_461del | p.Ile153_Leu154delinsMet | inframe_deletion | 3/3 | ENST00000327047.6 | NP_777367.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLRN1 | ENST00000327047.6 | c.459_461del | p.Ile153_Leu154delinsMet | inframe_deletion | 3/3 | 1 | NM_174878.3 | ENSP00000322280 | P1 | |
ENST00000469268.1 | n.235+37305_235+37307del | intron_variant, non_coding_transcript_variant | 4 | |||||||
CLRN1-AS1 | ENST00000476886.5 | n.123+75569_123+75571del | 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: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Usher syndrome type 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
Retinitis pigmentosa 61 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 19, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 28
Find out detailed SpliceAI scores and Pangolin per-transcript scores at