3-150928173-CAAT-C

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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 8.17
Variant links:
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]
CLRN1-AS1 (HGNC:30895): (CLRN1 antisense RNA 1)

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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
CLRN1NM_174878.3 linkuse as main transcriptc.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
CLRN1ENST00000327047.6 linkuse as main transcriptc.459_461del p.Ile153_Leu154delinsMet inframe_deletion 3/31 NM_174878.3 ENSP00000322280 P1P58418-3
ENST00000469268.1 linkuse as main transcriptn.235+37305_235+37307del intron_variant, non_coding_transcript_variant 4
CLRN1-AS1ENST00000476886.5 linkuse as main transcriptn.123+75569_123+75571del intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 providedliterature onlyOMIMSep 01, 2002- -
Retinitis pigmentosa 61 Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingBaylor GeneticsNov 19, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: 28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1085307049; hg19: chr3-150645960; API