5-41382145-T-C

Position:

• chr5-41382145-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005473.3(PLCXD3):​c.493A>G​(p.Ile165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: PLCXD3 NM_001005473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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]

ACMG classification

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=0.09788111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCXD3	NM_001005473.3	c.493A>G	p.Ile165Val	missense_variant	2/3	ENST00000377801.8
PLCXD3	XM_017009438.3	c.277A>G	p.Ile93Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCXD3	ENST00000377801.8	c.493A>G	p.Ile165Val	missense_variant	2/3	1	NM_001005473.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

The c.493A>G (p.I165V) 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 493, causing the isoleucine (I) at amino acid position 165 to be replaced by a valine (V). 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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.57
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.53	N;N
MutationTaster	Benign	0.90	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.12
Sift	Benign	0.93	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.053
MutPred		0.55		Loss of catalytic residue at I165 (P = 0.0396);Loss of catalytic residue at I165 (P = 0.0396);
MVP		0.23
MPC		0.076
ClinPred		0.52	D
GERP RS		5.8
Varity_R		0.070
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-41382247;