NM_006225.4:c.*234delC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006225.4(PLCD1):​c.*234delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 675,396 control chromosomes in the GnomAD database, including 12,919 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4480 hom., cov: 28)
  • Exomes 𝑓: 0.16 (8439 hom.)
• Consequence: PLCD1 NM_006225.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.494
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-38007538-TG-T is Benign according to our data. Variant chr3-38007538-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1275453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

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.*234delC		3_prime_UTR	Exon 15 of 15	NP_006216.2	A0A384MR47
	PLCD1	NM_001130964.2		c.*234delC		3_prime_UTR	Exon 15 of 15	NP_001124436.1	P51178-2
	PLCD1	NR_024071.2		n.2732delC		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.*234delC		3_prime_UTR	Exon 15 of 15	ENSP00000335600.4	P51178-1
	PLCD1	ENST00000463876.5	TSL:2	c.*234delC		3_prime_UTR	Exon 15 of 15	ENSP00000430344.1	P51178-2
	PLCD1	ENST00000956065.1		c.*234delC		3_prime_UTR	Exon 15 of 15	ENSP00000626124.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32671 AN: 151582 Hom.: 4462 Cov.: 28

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.149 AC: 19537 AN: 130904 AF XY: 0.155

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.0733

Gnomad ASJ exome AF: 0.0876

Gnomad EAS exome AF: 0.0787

Gnomad FIN exome AF: 0.0961

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.160 AC: 83914 AN: 523696 Hom.: 8439 Cov.: 0 AF XY: 0.165 AC XY: 46318 AN XY: 281268

African (AFR) AF: 0.381 AC: 5706 AN: 14976

American (AMR) AF: 0.0830 AC: 2776 AN: 33460

Ashkenazi Jewish (ASJ) AF: 0.0973 AC: 1889 AN: 19416

East Asian (EAS) AF: 0.0620 AC: 1932 AN: 31146

South Asian (SAS) AF: 0.250 AC: 15218 AN: 60872

European-Finnish (FIN) AF: 0.117 AC: 3838 AN: 32682

Middle Eastern (MID) AF: 0.173 AC: 404 AN: 2332

European-Non Finnish (NFE) AF: 0.158 AC: 47437 AN: 299806

Other (OTH) AF: 0.163 AC: 4714 AN: 29006

GnomAD4 genome AF: 0.216 AC: 32723 AN: 151700 Hom.: 4480 Cov.: 28 AF XY: 0.212 AC XY: 15705 AN XY: 74138

African (AFR) AF: 0.386 AC: 15907 AN: 41208

American (AMR) AF: 0.122 AC: 1863 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.0858 AC: 443 AN: 5162

South Asian (SAS) AF: 0.265 AC: 1271 AN: 4798

European-Finnish (FIN) AF: 0.113 AC: 1190 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11133 AN: 67906

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.176 Hom.: 560

Bravo AF: 0.222

Asia WGS AF: 0.175 AC: 609 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52184099; COSMIC: COSV52184099;