rs1394924865

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_015192.4(PLCB1):c.1711G>A(p.Val571Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PLCB1
NM_015192.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.15

Variant links:

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 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 many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PLCB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, PLCB1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4 linkuse as main transcript	c.1711G>A	p.Val571Met	missense_variant	17/32	ENST00000338037.11
PLCB1	NM_182734.3 linkuse as main transcript	c.1711G>A	p.Val571Met	missense_variant	17/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11 linkuse as main transcript	c.1711G>A	p.Val571Met	missense_variant	17/32	1	NM_015192.4	P1	Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151958

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453822

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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:

0.00000362

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 12

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 31, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	May 08, 2023	ClinVar contains an entry for this variant (Variation ID: 538884). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLCB1 protein function. This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0008%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 571 of the PLCB1 protein (p.Val571Met). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.020

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;.;D;D;D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.64

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.54

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

Polyphen

1.0, 0.99

.;.;D;D;D;.;.;.

Vest4

0.72, 0.64, 0.72

MutPred

0.47

.;.;Loss of phosphorylation at T573 (P = 0.0783);Loss of phosphorylation at T573 (P = 0.0783);Loss of phosphorylation at T573 (P = 0.0783);.;.;.;

MVP

0.73

MPC

2.3

ClinPred

0.99

GERP RS

5.9

Varity_R

0.13

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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