chr20-41166219-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_002660.3(PLCG1):c.1825C>T(p.Arg609Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,480 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PLCG1
NM_002660.3 missense
NM_002660.3 missense
Scores
9
7
2
Clinical Significance
Conservation
PhyloP100: 3.15
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 Likely_benign. Variant got -1 ACMG points.
PP2
Missense variant where missense usually causes diseases, PLCG1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.923
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG1 | NM_002660.3 | c.1825C>T | p.Arg609Cys | missense_variant | 17/32 | ENST00000685551.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG1 | ENST00000685551.1 | c.1825C>T | p.Arg609Cys | missense_variant | 17/32 | NM_002660.3 | P3 | ||
PLCG1 | ENST00000373271.5 | c.1825C>T | p.Arg609Cys | missense_variant | 17/32 | 1 | A1 | ||
PLCG1 | ENST00000244007.7 | c.1825C>T | p.Arg609Cys | missense_variant | 18/33 | 5 | P3 | ||
PLCG1 | ENST00000465571.2 | n.46C>T | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251060Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135758
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461480Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727072
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2021 | The c.1825C>T (p.R609C) alteration is located in exon 17 (coding exon 17) of the PLCG1 gene. This alteration results from a C to T substitution at nucleotide position 1825, causing the arginine (R) at amino acid position 609 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0118);Loss of MoRF binding (P = 0.0118);
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