3-53178196-C-A

Position:

• chr3-53178196-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000330452.8(PRKCD):​c.-19-208C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,194 control chromosomes in the GnomAD database, including 1,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.12 (1319 hom., cov: 31)
• Consequence: PRKCD ENST00000330452.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.194

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-53178196-C-A is Benign according to our data. Variant chr3-53178196-C-A is described in ClinVar as [Benign]. Clinvar id is 1268678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.-19-208C>A		intron_variant		ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8	c.-19-208C>A		intron_variant		1	NM_006254.4	ENSP00000331602	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18031 AN: 152076 Hom.: 1318 Cov.: 31

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.118 AC: 18028 AN: 152194 Hom.: 1319 Cov.: 31 AF XY: 0.116 AC XY: 8666 AN XY: 74428

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.120

Alfa AF: 0.150 Hom.: 219

Bravo AF: 0.111

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.71

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: rs112724859; hg19: chr3-53212212;