Genetic Variant PLCL1:p.Ala278Val (chr2-198084350-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/22 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

Publications

13 publications found

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:

ENSG00000305132 (HGNC:):

ENSG00000305132 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2651798.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	NM_006226.4	MANE Select	c.833C>T	p.Ala278Val	missense	Exon 2 of 6	NP_006217.3	Q15111-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.833C>T	p.Ala278Val	missense	Exon 2 of 6	ENSP00000402861.1	Q15111-1
PLCL1	ENST00000487695.6	TSL:5	c.611C>T	p.Ala204Val	missense	Exon 2 of 6	ENSP00000457588.1	H3BUD4
PLCL1	ENST00000435320.1	TSL:2	n.*605C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000410488.1	F8WAR2

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

GnomAD2 exomes

AF:

0.00208

AC:

522

AN:

250712

AF XY:

0.00196

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 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

African (AFR)

AF:

0.000508

AC:

AN:

33474

American (AMR)

AF:

0.000872

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000406

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00367

AC:

196

AN:

53406

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00365

AC:

4057

AN:

1111864

Other (OTH)

AF:

0.00209

AC:

126

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

229

457

686

914

1143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152260

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41546

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00344

AC:

234

AN:

68010

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00284

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.017

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

M_CAP

Benign

0.012

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

PhyloP100

4.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.087

Sift

Benign

0.23

Sift4G

Benign

0.33

Polyphen

0.0010

Vest4

0.074

MVP

0.45

MPC

0.32

ClinPred

0.015

GERP RS

5.7

Varity_R

0.15

gMVP

0.22

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over