rs397514480
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate
The NM_001377142.1(PLCB4):c.1904A>G(p.Tyr635Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PLCB4
NM_001377142.1 missense
NM_001377142.1 missense
Scores
15
1
1
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
PLCB4 (HGNC:9059): (phospholipase C beta 4) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals in the retina. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PLCB4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.98
PP5
?
Variant 20-9409086-A-G is Pathogenic according to our data. Variant chr20-9409086-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 31637.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-9409086-A-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCB4 | NM_001377142.1 | c.1904A>G | p.Tyr635Cys | missense_variant | 24/40 | ENST00000378473.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB4 | ENST00000378473.9 | c.1904A>G | p.Tyr635Cys | missense_variant | 24/40 | 1 | NM_001377142.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Auriculocondylar syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 04, 2012 | - - |
Auriculocondylar syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | University of Washington Center for Mendelian Genomics, University of Washington | Sep 17, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0
.;D;.;D;D
Vest4
MutPred
0.87
.;Loss of catalytic residue at I622 (P = 0.0561);.;Loss of catalytic residue at I622 (P = 0.0561);Loss of catalytic residue at I622 (P = 0.0561);
MVP
MPC
1.9
ClinPred
D
GERP RS
Varity_R
gMVP
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