chr11-33710247-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000611.6(CD59):c.266G>A(p.Cys89Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,822 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. C89C) has been classified as Likely benign.
Frequency
Consequence
NM_000611.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD59 | NM_000611.6 | c.266G>A | p.Cys89Tyr | missense_variant | 4/4 | ENST00000642928.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD59 | ENST00000642928.2 | c.266G>A | p.Cys89Tyr | missense_variant | 4/4 | NM_000611.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251404Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727222
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary CD59 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 03, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 15, 2023 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CD59 function (PMID: 23149847). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 64690). This missense change has been observed in individuals with CD59 deficiency (PMID: 23149847). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs397514767, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 89 of the CD59 protein (p.Cys89Tyr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at