chr20-9362934-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001377142.1(PLCB4):c.408C>A(p.Phe136Leu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
PLCB4
NM_001377142.1 missense
NM_001377142.1 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 1.94
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PLCB4. . Gene score misZ: 3.5718 (greater than the threshold 3.09). Trascript score misZ: 3.2758 (greater than threshold 3.09). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 18 curated benign missense variants. GenCC has associacion of the gene with auriculocondylar syndrome 1, auriculocondylar syndrome, auriculocondylar syndrome 2.
BP4
Computational evidence support a benign effect (MetaRNN=0.4029398).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCB4 | NM_001377142.1 | c.408C>A | p.Phe136Leu | missense_variant | 8/40 | ENST00000378473.9 | NP_001364071.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCB4 | ENST00000378473.9 | c.408C>A | p.Phe136Leu | missense_variant | 8/40 | 1 | NM_001377142.1 | ENSP00000367734.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.;N;N
REVEL
Benign
Sift
Benign
T;T;.;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.92, 0.0070
.;P;.;P;B
Vest4
MutPred
Gain of catalytic residue at F136 (P = 0.0479);Gain of catalytic residue at F136 (P = 0.0479);Gain of catalytic residue at F136 (P = 0.0479);Gain of catalytic residue at F136 (P = 0.0479);Gain of catalytic residue at F136 (P = 0.0479);
MVP
MPC
0.88
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