chr3-38008032-A-C

Position:

• chr3-38008032-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006225.4(PLCD1):​c.2167T>G​(p.Leu723Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCD1 NM_006225.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15437704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCD1	NM_006225.4	c.2167T>G	p.Leu723Val	missense_variant	14/15	ENST00000334661.5
PLCD1	NM_001130964.2	c.2230T>G	p.Leu744Val	missense_variant	14/15
PLCD1	NR_024071.2	n.2394T>G		non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCD1	ENST00000334661.5	c.2167T>G	p.Leu723Val	missense_variant	14/15	1	NM_006225.4	A1
PLCD1	ENST00000463876.5	c.2230T>G	p.Leu744Val	missense_variant	14/15	2		P3
PLCD1	ENST00000417185.6	n.304T>G		non_coding_transcript_exon_variant	1/2	2
PLCD1	ENST00000461445.5	n.2890T>G		non_coding_transcript_exon_variant	11/12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.2230T>G (p.L744V) alteration is located in exon 14 (coding exon 14) of the PLCD1 gene. This alteration results from a T to G substitution at nucleotide position 2230, causing the leucine (L) at amino acid position 744 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	.;L
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.036
Sift	Benign	0.15	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.067	.;B
Vest4		0.48
MutPred		0.46		.;Loss of glycosylation at S719 (P = 0.0766);
MVP		0.24
MPC		0.22
ClinPred		0.15	T
GERP RS		-2.2
Varity_R		0.059
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38049523;