Variant chr20-41160152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_002660.3(PLCG1):c.511C>T(p.Arg171Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000205 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLCG1
NM_002660.3 missense, splice_region

Scores

Splicing: ADA: 0.9652

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.03

Variant links:

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]

PLCG1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity PLCG1_HUMAN

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 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant, splice_region_variant	4/32	ENST00000685551.1	NP_002651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG1	ENST00000685551.1 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant, splice_region_variant	4/32		NM_002660.3	ENSP00000508698	P3	P19174-2
PLCG1	ENST00000373271.5 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant, splice_region_variant	4/32	1		ENSP00000362368	A1	P19174-1
PLCG1	ENST00000244007.7 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant, splice_region_variant	5/33	5		ENSP00000244007	P3	P19174-2
PLCG1	ENST00000483646.2 linkuse as main transcript	n.421C>T		splice_region_variant, non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000306

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLCG1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2024

The PLCG1 c.511C>T variant is predicted to result in the amino acid substitution p.Arg171Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

.;D

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.76

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.79

.;P

Vest4

0.56

MutPred

0.45

Loss of MoRF binding (P = 0.0027);Loss of MoRF binding (P = 0.0027);

MVP

0.63

ClinPred

0.79

GERP RS

4.0

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.10

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over