3-53164998-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006254.4(PRKCD):c.-131-106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,060 control chromosomes in the GnomAD database, including 46,589 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 0.78 (46572 hom., cov: 31)
  • Exomes 𝑓: 0.90 (17 hom.)
• Consequence: PRKCD NM_006254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

PRKCD (HGNC:9399): (protein kinase C delta) The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCD	NM_006254.4	c.-131-106T>G		intron_variant		ENST00000330452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCD	ENST00000330452.8	c.-131-106T>G		intron_variant		1	NM_006254.4	P1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117812 AN: 151900 Hom.: 46560 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.905 AC: 38 AN: 42 Hom.: 17 AF XY: 0.900 AC XY: 27 AN XY: 30

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.967

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.775 AC: 117865 AN: 152018 Hom.: 46572 Cov.: 31 AF XY: 0.779 AC XY: 57845 AN XY: 74292

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.791

Alfa AF: 0.828 Hom.: 72758

Bravo AF: 0.757

Asia WGS AF: 0.801 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.7
Dann	Benign	0.74

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: rs1483185; hg19: chr3-53199014;