Genetic Variant PLCXD3:p.Ser197Gly (chr5-41382049-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005473.3(PLCXD3):c.589A>G(p.Ser197Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PLCXD3
NM_001005473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

Publications

0 publications found

Variant links:

Genes affected

PLCXD3 (HGNC:31822): (phosphatidylinositol specific phospholipase C X domain containing 3) Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in cytoplasm. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

PLCXD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21210247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCXD3	NM_001005473.3 link	c.589A>G	p.Ser197Gly	missense_variant	Exon 2 of 3	ENST00000377801.8	NP_001005473.1	Q63HM9B3KXD1
PLCXD3	XM_017009438.3 link	c.373A>G	p.Ser125Gly	missense_variant	Exon 2 of 3		XP_016864927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCXD3	ENST00000377801.8 link	c.589A>G	p.Ser197Gly	missense_variant	Exon 2 of 3	1	NM_001005473.3	ENSP00000367032.3		Q63HM9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111756

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 30, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.589A>G (p.S197G) alteration is located in exon 2 (coding exon 2) of the PLCXD3 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the serine (S) at amino acid position 197 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.027

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.0027

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

L;L

PhyloP100

4.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.055

Sift

Benign

0.40

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.075

B;B

Vest4

0.52

MutPred

0.43

Loss of stability (P = 0.1223);Loss of stability (P = 0.1223);

MVP

0.28

MPC

0.093

ClinPred

0.54

GERP RS

5.8

Varity_R

0.33

gMVP

0.48

Mutation Taster

=49/51

disease causing

(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.

chr5-41382049-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over