3-38007538-TG-TGG

Variant names:

• chr3-38007538-T-TG
• rs57208122
• NM_006225.4:c.*234dupC

Variant summary

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

The NM_006225.4(PLCD1):​c.*234dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: PLCD1 NM_006225.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• 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: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.*234dupC		3_prime_UTR	Exon 15 of 15	NP_006216.2	A0A384MR47
	PLCD1	NM_001130964.2		c.*234dupC		3_prime_UTR	Exon 15 of 15	NP_001124436.1	P51178-2
	PLCD1	NR_024071.2		n.2732dupC		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD1	ENST00000334661.5	TSL:1 MANE Select	c.*234dupC		3_prime_UTR	Exon 15 of 15	ENSP00000335600.4	P51178-1
	PLCD1	ENST00000463876.5	TSL:2	c.*234dupC		3_prime_UTR	Exon 15 of 15	ENSP00000430344.1	P51178-2
	PLCD1	ENST00000956065.1		c.*234dupC		3_prime_UTR	Exon 15 of 15	ENSP00000626124.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.49

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

dbSNP: rs57208122; hg19: chr3-38049029;