Variant 2-198084484-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 NM_006226.4(PLCL1):c.967A>G(p.Ile323Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PLCL1
NM_006226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

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:

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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=0.22618532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4 linkuse as main transcript	c.967A>G	p.Ile323Val	missense_variant	2/6	ENST00000428675.6	NP_006217.3	Q15111-1
PLCL1	XM_005246643.5 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	2/6		XP_005246700.1
PLCL1	XM_005246644.5 linkuse as main transcript	c.730A>G	p.Ile244Val	missense_variant	2/6		XP_005246701.1
PLCL1	XM_017004339.3 linkuse as main transcript	c.730A>G	p.Ile244Val	missense_variant	2/6		XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLCL1	ENST00000428675.6 linkuse as main transcript	c.967A>G	p.Ile323Val	missense_variant	2/6	1	NM_006226.4	ENSP00000402861.1	Q15111-1
PLCL1	ENST00000487695.6 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	2/6	5		ENSP00000457588.1	H3BUD4
PLCL1	ENST00000435320.1 linkuse as main transcript	n.*739A>G		non_coding_transcript_exon_variant	3/7	2		ENSP00000410488.1	F8WAR2
PLCL1	ENST00000435320.1 linkuse as main transcript	n.*739A>G		3_prime_UTR_variant	3/7	2		ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250892

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727186

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:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Nov 13, 2024

The c.967A>G (p.I323V) 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 967, causing the isoleucine (I) at amino acid position 323 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0053

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.52

N;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.010

D;D;.

Sift4G

Uncertain

0.033

D;D;D

Polyphen

0.30

B;.;.

Vest4

0.27

MutPred

0.62

Gain of ubiquitination at K325 (P = 0.0661);.;.;

MVP

0.14

MPC

0.44

ClinPred

0.27

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.22

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