Variant 2-198084653-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000428675.6(PLCL1):c.1136A>G(p.Gln379Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PLCL1
ENST00000428675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

Variant links:

Genes affected

PLCL1 (HGNC:9063): (phospholipase C like 1 (inactive)) Predicted to enable phospholipase C activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including gamma-aminobutyric acid signaling pathway; regulation of GABAergic synaptic transmission; and regulation of peptidyl-serine phosphorylation. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLCL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12923074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLCL1	NM_006226.4 linkuse as main transcript	c.1136A>G	p.Gln379Arg	missense_variant	2/6	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5 linkuse as main transcript	c.914A>G	p.Gln305Arg	missense_variant	2/6		XP_005246700.1
PLCL1	XM_005246644.5 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	2/6		XP_005246701.1
PLCL1	XM_017004339.3 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	2/6		XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6 linkuse as main transcript	c.1136A>G	p.Gln379Arg	missense_variant	2/6	1	NM_006226.4	ENSP00000402861	P1	Q15111-1
PLCL1	ENST00000487695.6 linkuse as main transcript	c.914A>G	p.Gln305Arg	missense_variant	2/6	5		ENSP00000457588
PLCL1	ENST00000435320.1 linkuse as main transcript	c.*908A>G		3_prime_UTR_variant, NMD_transcript_variant	3/7	2		ENSP00000410488

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251206

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Feb 17, 2024

The c.1136A>G (p.Q379R) alteration is located in exon 2 (coding exon 2) of the PLCL1 gene. This alteration results from a A to G substitution at nucleotide position 1136, causing the glutamine (Q) at amino acid position 379 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.036

T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.1

N;.;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.38

N;N;.

REVEL

Benign

0.090

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0090

B;.;.

Vest4

0.24

MutPred

0.54

Gain of phosphorylation at T378 (P = 0.1267);.;.;

MVP

0.088

MPC

0.35

ClinPred

0.050

GERP RS

4.8

Varity_R

0.12

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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