rs1554939509
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000611.6(CD59):c.190T>G(p.Cys64Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CD59
NM_000611.6 missense
NM_000611.6 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 3.50
Publications
1 publications found
Genes affected
CD59 (HGNC:1689): (CD59 molecule (CD59 blood group)) This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
CD59 Gene-Disease associations (from GenCC):
- primary CD59 deficiencyInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary CD59 deficiency Uncertain:1
May 03, 2020
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Benign
DEOGEN2
Pathogenic
.;D;D;D;D;D;D;D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;.;.;.;.;.;.;.;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;M;M;M;M;M;M;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;.;D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;D;D;D;D;D;D;D;.
Vest4
MutPred
Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);Loss of methylation at K63 (P = 0.0152);
MVP
MPC
0.76
ClinPred
D
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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