rs373208120
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_174878.3(CLRN1):c.619C>T(p.Arg207Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000304 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R207R) has been classified as Likely benign.
Frequency
Consequence
NM_174878.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLRN1 | NM_174878.3 | c.619C>T | p.Arg207Ter | stop_gained | 3/3 | ENST00000327047.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLRN1 | ENST00000327047.6 | c.619C>T | p.Arg207Ter | stop_gained | 3/3 | 1 | NM_174878.3 | P1 | |
ENST00000469268.1 | n.235+37146G>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLRN1-AS1 | ENST00000476886.5 | n.123+75410G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251112Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135708
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 727228
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Usher syndrome type 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 02, 2016 | - - |
Retinitis pigmentosa;C3280041:Retinitis pigmentosa 61;C5779850:Usher syndrome type 3A Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 16, 2021 | - - |
Retinitis pigmentosa 61 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 05, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change creates a premature translational stop signal (p.Arg207*) in the CLRN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the CLRN1 protein. This variant is present in population databases (rs373208120, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 22952768, 23304067, 26338283). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.C658T (p.R220X). ClinVar contains an entry for this variant (Variation ID: 371628). For these reasons, this variant has been classified as Pathogenic. - |
Usher syndrome type 3A Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at