NM_001005473.3:c.663C>A

Variant names:

• chr5-41381975-G-T
• rs565958730
• NM_001005473.3:c.663C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001005473.3(PLCXD3):​c.663C>A​(p.Asp221Glu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCXD3 NM_001005473.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3259639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCXD3	NM_001005473.3	c.663C>A	p.Asp221Glu	missense_variant	Exon 2 of 3	ENST00000377801.8	NP_001005473.1
PLCXD3	XM_017009438.3	c.447C>A	p.Asp149Glu	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	c.663C>A	p.Asp221Glu	missense_variant	Exon 2 of 3	1	NM_001005473.3	ENSP00000367032.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.59	N;N
PhyloP100		2.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.13
Sift	Benign	0.91	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.98	D;D
Vest4		0.56
MutPred		0.28		Gain of disorder (P = 0.1039);Gain of disorder (P = 0.1039);
MVP		0.21
MPC		0.094
ClinPred		0.77	D
GERP RS		4.9
Varity_R		0.089
gMVP		0.50
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs565958730; hg19: chr5-41382077;