chr3-38007831-T-C

Variant names:

• chr3-38007831-T-C
• NM_006225.4:c.2213A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006225.4(PLCD1):​c.2213A>G​(p.Lys738Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCD1 NM_006225.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

Genes affected

PLCD1 (HGNC:9060): (phospholipase C delta 1) This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD1	NM_006225.4	c.2213A>G	p.Lys738Arg	missense_variant	Exon 15 of 15	ENST00000334661.5	NP_006216.2
PLCD1	NM_001130964.2	c.2276A>G	p.Lys759Arg	missense_variant	Exon 15 of 15		NP_001124436.1
PLCD1	NR_024071.2	n.2440A>G		non_coding_transcript_exon_variant	Exon 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD1	ENST00000334661.5	c.2213A>G	p.Lys738Arg	missense_variant	Exon 15 of 15	1	NM_006225.4	ENSP00000335600.4
PLCD1	ENST00000463876.5	c.2276A>G	p.Lys759Arg	missense_variant	Exon 15 of 15	2		ENSP00000430344.1
PLCD1	ENST00000417185.6	n.350A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
PLCD1	ENST00000461445.5	n.2936A>G		non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2276A>G (p.K759R) alteration is located in exon 15 (coding exon 15) of the PLCD1 gene. This alteration results from a A to G substitution at nucleotide position 2276, causing the lysine (K) at amino acid position 759 to be replaced by an arginine (R). 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	0.064
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	0.014
Eigen_PC	Benign	0.0026
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.050
Sift	Benign	0.13	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.99	.;D
Vest4		0.23
MutPred		0.33		.;Loss of ubiquitination at K738 (P = 0.0141);
MVP		0.51
MPC		0.20
ClinPred		0.75	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38049322;