NM_032726.4:c.298T>G

Variant names:

• chr2-218618695-T-G
• NM_032726.4:c.298T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032726.4(PLCD4):​c.298T>G​(p.Ser100Ala) 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. 17/22 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: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17096993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.298T>G	p.Ser100Ala	missense_variant	Exon 4 of 16	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.298T>G	p.Ser100Ala	missense_variant	Exon 4 of 16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.298T>G	p.Ser100Ala	missense_variant	Exon 4 of 17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.298T>G	p.Ser100Ala	missense_variant	Exon 4 of 17	5		ENSP00000396942.1
PLCD4	ENST00000444453.5	n.195T>G		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000415725.1
PLCD4	ENST00000446503.5	n.195T>G		non_coding_transcript_exon_variant	Exon 4 of 6	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

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298T>G (p.S100A) alteration is located in exon 4 (coding exon 3) of the PLCD4 gene. This alteration results from a T to G substitution at nucleotide position 298, causing the serine (S) at amino acid position 100 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.46	T;.;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.83	N;N;N
REVEL	Benign	0.065
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.22
MutPred		0.40		Loss of phosphorylation at S100 (P = 0.0823);Loss of phosphorylation at S100 (P = 0.0823);Loss of phosphorylation at S100 (P = 0.0823);
MVP		0.38
MPC		0.19
ClinPred		0.10	T
GERP RS		-3.8
Varity_R		0.065
gMVP		0.13
Mutation Taster		=99/1	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

hg19: chr2-219483418;