rs12946454

Variant names:

• chr17-45130754-A-T
• rs12946454
• NM_133373.5:c.163+1494T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133373.5(PLCD3):​c.163+1494T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,592 control chromosomes in the GnomAD database, including 3,762 homozygotes. 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: 𝑓 0.21 (3762 hom., cov: 31)
• Consequence: PLCD3 NM_133373.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 84 publications found

Genes affected

PLCD3 (HGNC:9061): (phospholipase C delta 3) This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate the second messengers diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diacylglycerol and IP3 mediate a variety of cellular responses to extracellular stimuli by inducing protein kinase C and increasing cytosolic Ca(2+) concentrations. This enzyme localizes to the plasma membrane and requires calcium for activation. Its activity is inhibited by spermine, sphingosine, and several phospholipids. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133373.5. 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
	PLCD3	NM_133373.5	MANE Select	c.163+1494T>A		intron	N/A	NP_588614.1	Q8N3E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD3	ENST00000619929.5	TSL:1 MANE Select	c.163+1494T>A		intron	N/A	ENSP00000479636.1	Q8N3E9
	PLCD3	ENST00000590644.5	TSL:4	c.94+2497T>A		intron	N/A	ENSP00000467800.1	K7EQF2
	PLCD3	ENST00000538093.1	TSL:4	c.-30+2324T>A		intron	N/A	ENSP00000440378.1	F5GXC1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31573 AN: 151474 Hom.: 3763 Cov.: 31

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31569 AN: 151592 Hom.: 3762 Cov.: 31 AF XY: 0.211 AC XY: 15661 AN XY: 74060

African (AFR) AF: 0.0918 AC: 3797 AN: 41348

American (AMR) AF: 0.216 AC: 3287 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1054 AN: 5114

South Asian (SAS) AF: 0.298 AC: 1430 AN: 4796

European-Finnish (FIN) AF: 0.252 AC: 2646 AN: 10520

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17627 AN: 67820

Other (OTH) AF: 0.210 AC: 440 AN: 2094

Alfa AF: 0.225 Hom.: 530

Bravo AF: 0.201

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.19
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: rs12946454; hg19: chr17-43208121;