3-111713984-G-T

Position:

• chr3-111713984-G-T

Variant summary

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

The ENST00000477665.2(PLCXD2):​c.722G>T​(p.Arg241Leu) 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. 15/20 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: PLCXD2 ENST00000477665.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.660

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]

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=0.07748315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCXD2	NM_001413064.1	c.722G>T	p.Arg241Leu	missense_variant	3/4		NP_001399993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCXD2	ENST00000477665.2	c.722G>T	p.Arg241Leu	missense_variant	3/5	1	NM_001185106.1	ENSP00000420686.1
PLCXD2	ENST00000636933.2	c.722G>T	p.Arg241Leu	missense_variant	3/4	5		ENSP00000490816.1
PLCXD2	ENST00000393934.7	c.722G>T	p.Arg241Leu	missense_variant	3/4	1		ENSP00000377511.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 06, 2024

The c.722G>T (p.R241L) alteration is located in exon 3 (coding exon 3) of the PLCXD2 gene. This alteration results from a G to T substitution at nucleotide position 722, causing the arginine (R) at amino acid position 241 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.6
DANN	Benign	0.95
DEOGEN2	Benign	0.078	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	.;N;N
REVEL	Benign	0.039
Sift	Benign	0.28	.;T;T
Sift4G	Benign	0.16	.;T;T
Polyphen		0.019, 0.0080	.;B;B
Vest4		0.39
MutPred		0.53		Gain of ubiquitination at K242 (P = 0.0554);Gain of ubiquitination at K242 (P = 0.0554);Gain of ubiquitination at K242 (P = 0.0554);
MVP		0.030
MPC		0.15
ClinPred		0.058	T
GERP RS		-1.6
Varity_R		0.065
gMVP		0.28

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

Other links and lift over

dbSNP: rs776985841; hg19: chr3-111432831;