chr17-45130754-A-T

Position:

• chr17-45130754-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

PLCD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCD3	NM_133373.5	c.163+1494T>A		intron_variant		ENST00000619929.5	NP_588614.1
PLCD3	XM_024450554.2	c.163+1494T>A		intron_variant			XP_024306322.1
PLCD3	XM_011524253.4	c.163+1494T>A		intron_variant			XP_011522555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCD3	ENST00000619929.5	c.163+1494T>A		intron_variant		1	NM_133373.5	ENSP00000479636.1
PLCD3	ENST00000590644.5	c.94+2497T>A		intron_variant		4		ENSP00000467800.1
PLCD3	ENST00000538093.1	c.-30+2324T>A		intron_variant		4		ENSP00000440378.1
PLCD3	ENST00000544446.1	n.272-1468T>A		intron_variant		4

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

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.210

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs12946454; hg19: chr17-43208121;