PLCD1 p.Gln671His

Variant names:

• chr3-38008257-C-A
• NM_006225.4:c.2013G>T
• PLCD1 p.Gln671His

Your query was ambiguous. Multiple possible variants found:

• chr3-38008257-C-A
• chr3-38008257-C-G

Variant summary

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

The NM_006225.4(PLCD1):​c.2013G>T​(p.Gln671His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCD1 NM_006225.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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]

PLCD1 Gene-Disease associations (from GenCC):

• nonsyndromic congenital nail disorder 3

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

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=0.34030932).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006225.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD1	NM_006225.4	MANE Select	c.2013G>T	p.Gln671His	missense	Exon 13 of 15	NP_006216.2	A0A384MR47
	PLCD1	NM_001130964.2		c.2076G>T	p.Gln692His	missense	Exon 13 of 15	NP_001124436.1	P51178-2
	PLCD1	NR_024071.2		n.2240G>T		non_coding_transcript_exon	Exon 12 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD1	ENST00000334661.5	TSL:1 MANE Select	c.2013G>T	p.Gln671His	missense	Exon 13 of 15	ENSP00000335600.4	P51178-1
	PLCD1	ENST00000463876.5	TSL:2	c.2076G>T	p.Gln692His	missense	Exon 13 of 15	ENSP00000430344.1	P51178-2
	PLCD1	ENST00000956065.1		c.2010G>T	p.Gln670His	missense	Exon 13 of 15	ENSP00000626124.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.036	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.52
Mutation Taster		=86/14	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-38049748;