Variant 2-198084350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006226.4(PLCL1):c.833C>T(p.Ala278Val) variant causes a missense change. The variant allele was found at a frequency of 0.00296 in 1,613,972 control chromosomes in the GnomAD database, including 12 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 12 hom. )

Consequence

PLCL1
NM_006226.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.95

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0079678595).

BP6

Variant 2-198084350-C-T is Benign according to our data. Variant chr2-198084350-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651798.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLCL1	NM_006226.4 linkuse as main transcript	c.833C>T	p.Ala278Val	missense_variant	2/6	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5 linkuse as main transcript	c.611C>T	p.Ala204Val	missense_variant	2/6		XP_005246700.1
PLCL1	XM_005246644.5 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	2/6		XP_005246701.1
PLCL1	XM_017004339.3 linkuse as main transcript	c.596C>T	p.Ala199Val	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.833C>T	p.Ala278Val	missense_variant	2/6	1	NM_006226.4	ENSP00000402861	P1	Q15111-1
PLCL1	ENST00000487695.6 linkuse as main transcript	c.611C>T	p.Ala204Val	missense_variant	2/6	5		ENSP00000457588
PLCL1	ENST00000435320.1 linkuse as main transcript	c.*605C>T		3_prime_UTR_variant, NMD_transcript_variant	3/7	2		ENSP00000410488

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00208

AC:

522

AN:

250712

Hom.:

AF XY:

0.00196

AC XY:

265

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00286

Gnomad NFE exome

AF:

0.00358

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00307

AC:

4486

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

2171

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00367

Gnomad4 NFE exome

AF:

0.00365

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152260

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00197

AC:

239

EpiCase

AF:

0.00289

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

PLCL1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.017

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0080

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

N;.;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.087

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.074

MVP

0.45

MPC

0.32

ClinPred

0.015

GERP RS

5.7

Varity_R

0.15

gMVP

0.22

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

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