NM_032726.4:c.94T>G

Variant names:

• chr2-218615975-T-G
• NM_032726.4:c.94T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032726.4(PLCD4):​c.94T>G​(p.Trp32Gly) 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: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68
• Publications: 0 publications found

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.94T>G	p.Trp32Gly	missense_variant	Exon 3 of 16	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.94T>G	p.Trp32Gly	missense_variant	Exon 3 of 16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.94T>G	p.Trp32Gly	missense_variant	Exon 3 of 17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.94T>G	p.Trp32Gly	missense_variant	Exon 3 of 17	5		ENSP00000396942.1
PLCD4	ENST00000444453.5	n.78+16T>G		intron_variant	Intron 3 of 4	4		ENSP00000415725.1
PLCD4	ENST00000446503.5	n.78+16T>G		intron_variant	Intron 3 of 5	4		ENSP00000406040.1

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

Apr 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94T>G (p.W32G) alteration is located in exon 3 (coding exon 2) of the PLCD4 gene. This alteration results from a T to G substitution at nucleotide position 94, causing the tryptophan (W) at amino acid position 32 to be replaced by a glycine (G). 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	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.65	D;D;.;D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;T;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Uncertain	0.043	D
MutationAssessor	Uncertain	2.9	M;M;.;.
PhyloP100		7.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-11	D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.69
MutPred		0.55		Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);
MVP		0.89
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.80
gMVP		0.66
Mutation Taster		=23/77	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr2-219480698;