5-41381919-C-A

Variant summary

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

The NM_001005473.3(PLCXD3):​c.719G>T​(p.Gly240Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

PLCXD3
NM_001005473.3 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45
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]

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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, 0.832

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCXD3NM_001005473.3 linkc.719G>T p.Gly240Val missense_variant Exon 2 of 3 ENST00000377801.8 NP_001005473.1 Q63HM9B3KXD1
PLCXD3XM_017009438.3 linkc.503G>T p.Gly168Val missense_variant Exon 2 of 3 XP_016864927.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCXD3ENST00000377801.8 linkc.719G>T p.Gly240Val missense_variant Exon 2 of 3 1 NM_001005473.3 ENSP00000367032.3 Q63HM9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.719G>T (p.G240V) alteration is located in exon 2 (coding exon 2) of the PLCXD3 gene. This alteration results from a G to T substitution at nucleotide position 719, causing the glycine (G) at amino acid position 240 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
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Uncertain
-0.062
T
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.017
D;D
Sift4G
Uncertain
0.027
D;D
Polyphen
1.0
D;D
Vest4
0.96
MutPred
0.65
Loss of disorder (P = 0.0689);Loss of disorder (P = 0.0689);
MVP
0.27
MPC
0.53
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.61
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.48
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.48
Position offset: 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.

Other links and lift over

dbSNP: rs1170281413; hg19: chr5-41382021; API