Variant 3-111707945-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000477665.2(PLCXD2):c.183C>G(p.Ser61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PLCXD2
ENST00000477665.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.713

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCXD2	NM_001413064.1 linkuse as main transcript	c.183C>G	p.Ser61Arg	missense_variant	2/4	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.183C>G	p.Ser61Arg	missense_variant	2/4	5	NM_001413064.1	ENSP00000490816	P1
PLCXD2	ENST00000477665.2 linkuse as main transcript	c.183C>G	p.Ser61Arg	missense_variant	2/5	1		ENSP00000420686		Q0VAA5-1
PLCXD2	ENST00000393934.7 linkuse as main transcript	c.183C>G	p.Ser61Arg	missense_variant	2/4	1		ENSP00000377511		Q0VAA5-2
PLCXD2	ENST00000468174.1 linkuse as main transcript	n.223C>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250418

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135358

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461368

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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.183C>G (p.S61R) alteration is located in exon 2 (coding exon 2) of the PLCXD2 gene. This alteration results from a C to G substitution at nucleotide position 183, causing the serine (S) at amino acid position 61 to be replaced by an arginine (R). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.1

.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.6

.;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.0030

.;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.88, 0.88

MutPred

0.72

Gain of catalytic residue at S61 (P = 0.0452);Gain of catalytic residue at S61 (P = 0.0452);Gain of catalytic residue at S61 (P = 0.0452);

MVP

0.13

MPC

0.57

ClinPred

0.97

GERP RS

4.0

Varity_R

0.57

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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