rs763783966

Variant names:

• chr5-41381880-G-A
• rs763783966
• NM_001005473.3:c.758C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-41381880-G-A
• chr5-41381880-G-C

Variant summary

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

The NM_001005473.3(PLCXD3):​c.758C>T​(p.Ala253Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A253G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLCXD3 NM_001005473.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40
• 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=0.26537558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCXD3	NM_001005473.3	c.758C>T	p.Ala253Val	missense_variant	Exon 2 of 3	ENST00000377801.8	NP_001005473.1
PLCXD3	XM_017009438.3	c.542C>T	p.Ala181Val	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.758C>T	p.Ala253Val	missense_variant	Exon 2 of 3	1	NM_001005473.3	ENSP00000367032.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461012 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726816

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111680

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.19	N;N
PhyloP100		6.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.22	N;N
REVEL	Uncertain	0.29
Sift	Benign	1.0	T;T
Sift4G	Benign	0.85	T;T
Polyphen		0.99	D;D
Vest4		0.38
MutPred		0.31		Gain of methylation at K252 (P = 0.0401);Gain of methylation at K252 (P = 0.0401);
MVP		0.24
MPC		0.12
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.27
gMVP		0.60
Mutation Taster		=55/45	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: rs763783966; hg19: chr5-41381982;