2-96287959-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 10P and 5B. PM1PM5PP2PP3_StrongPP5BS1_SupportingBS2
The NM_014014.5(SNRNP200):c.3269G>A(p.Arg1090Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1090L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_014014.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNRNP200 | ENST00000323853.10 | c.3269G>A | p.Arg1090Gln | missense_variant | 25/45 | 1 | NM_014014.5 | ENSP00000317123.5 | ||
SNRNP200 | ENST00000652267.1 | c.3269G>A | p.Arg1090Gln | missense_variant | 27/32 | ENSP00000498933.1 | ||||
SNRNP200 | ENST00000480615.1 | n.386G>A | non_coding_transcript_exon_variant | 5/10 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251470Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1360981). This missense change has been observed in individual(s) with autosomal recessive inherited retinal dystrophy (PMID: 29320387). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs397514574, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1090 of the SNRNP200 protein (p.Arg1090Gln). - |
Retinitis pigmentosa 33 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Pangenia Genomics, Pangenia Inc. | Jan 14, 2022 | The SNRNP200, c.3269G>A (p.Arg1090Gln) variant is at extremely low frequency in population databases ; allele frequency in East Asia population is 0.0001 by gnomAD v2.1.1. This missense variant results in the amino acid change of p.Arg1090Gln . Another variant resulting in the amino acid change at the same position to a different residue (p.Arg1090Leu ) has been determined to be pathogenic [PMID: 19710410]. In a 4-generation Chinese family with 12 members affected by autosomal dominant retinitis pigmentosa (RP), the heterozygous variant segregated with the disease and was not found in 100 ethnically matched controls. Multiple lines of computational evidence support a deleterious effect on the gene or gene product REVEL=0. 838. There is co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. This variant has also been detected in a consanguineous Pakistani family [PMID: 29320387 ], co-segregating with an autosomal recessive form of retinitis pigmentosa. - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at