NM_002660.3:c.1186A>C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_002660.3(PLCG1):āc.1186A>Cā(p.Thr396Pro) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.00043 ( 0 hom., cov: 31)
Exomes š: 0.000020 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PLCG1
NM_002660.3 missense
NM_002660.3 missense
Scores
10
8
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.52
Genes affected
PLCG1 (HGNC:9065): (phospholipase C gamma 1) 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 receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.953
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCG1 | ENST00000685551.1 | c.1186A>C | p.Thr396Pro | missense_variant | Exon 12 of 32 | NM_002660.3 | ENSP00000508698.1 | |||
PLCG1 | ENST00000373271.5 | c.1186A>C | p.Thr396Pro | missense_variant | Exon 12 of 32 | 1 | ENSP00000362368.1 | |||
PLCG1 | ENST00000244007.7 | c.1186A>C | p.Thr396Pro | missense_variant | Exon 13 of 33 | 5 | ENSP00000244007.3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 67AN: 151740Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 genomes
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31
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000199 AC: 29AN: 1458612Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 725654
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000435 AC: 66AN: 151862Hom.: 0 Cov.: 31 AF XY: 0.000431 AC XY: 32AN XY: 74246
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
T;T
Polyphen
P;P
Vest4
MutPred
Gain of methylation at K398 (P = 0.11);Gain of methylation at K398 (P = 0.11);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at