20-41162529-G-T

Position:

• chr20-41162529-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002660.3(PLCG1):​c.590G>T​(p.Arg197Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLCG1 NM_002660.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG1	NM_002660.3	c.590G>T	p.Arg197Leu	missense_variant	5/32	ENST00000685551.1	NP_002651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG1	ENST00000685551.1	c.590G>T	p.Arg197Leu	missense_variant	5/32		NM_002660.3	ENSP00000508698	P3
PLCG1	ENST00000373271.5	c.590G>T	p.Arg197Leu	missense_variant	5/32	1		ENSP00000362368	A1
PLCG1	ENST00000244007.7	c.590G>T	p.Arg197Leu	missense_variant	6/33	5		ENSP00000244007	P3
PLCG1	ENST00000483646.2	n.578G>T		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.20
Sift	Benign	0.68	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.0020	.;B
Vest4		0.68
MutPred		0.56		Loss of MoRF binding (P = 0.0373);Loss of MoRF binding (P = 0.0373);
MVP		0.56
ClinPred		0.83	D
GERP RS		5.0
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.19
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-39791169; COSMIC: COSV54817523; COSMIC: COSV54817523;