Variant 3-111713911-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000477665.2(PLCXD2):c.649T>A(p.Phe217Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

PLCXD2
ENST00000477665.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

PLCXD2 (HGNC:26462): (phosphatidylinositol specific phospholipase C X domain containing 2) Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PLCXD2 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=0.14317787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCXD2	NM_001413064.1 linkuse as main transcript	c.649T>A	p.Phe217Ile	missense_variant	3/4	ENST00000636933.2	NP_001399993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCXD2	ENST00000636933.2 linkuse as main transcript	c.649T>A	p.Phe217Ile	missense_variant	3/4	5	NM_001413064.1	ENSP00000490816	P1
PLCXD2	ENST00000477665.2 linkuse as main transcript	c.649T>A	p.Phe217Ile	missense_variant	3/5	1		ENSP00000420686		Q0VAA5-1
PLCXD2	ENST00000393934.7 linkuse as main transcript	c.649T>A	p.Phe217Ile	missense_variant	3/4	1		ENSP00000377511		Q0VAA5-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251178

Hom.:

AF XY:

0.0000221

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:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727084

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:

0.0000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 17, 2024

The c.649T>A (p.F217I) alteration is located in exon 3 (coding exon 3) of the PLCXD2 gene. This alteration results from a T to A substitution at nucleotide position 649, causing the phenylalanine (F) at amino acid position 217 to be replaced by an isoleucine (I). 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

0.091

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

.;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.44

.;N;N

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.65

.;N;N

REVEL

Benign

0.15

Sift

Benign

0.35

.;T;T

Sift4G

Benign

0.71

.;T;T

Polyphen

0.25, 0.33

.;B;B

Vest4

0.36

MVP

0.030

MPC

0.16

ClinPred

0.16

GERP RS

3.1

Varity_R

0.086

gMVP

0.24

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