3-53178196-C-A

Variant names:

• chr3-53178196-C-A
• rs112724859
• NM_006254.4:c.-19-208C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006254.4(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 NM_006254.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.194
• Publications: 2 publications found

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]

PRKCD Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal systemic lupus erythematosus type 16

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.-19-208C>A		intron_variant	Intron 2 of 18	ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8	c.-19-208C>A		intron_variant	Intron 2 of 18	1	NM_006254.4	ENSP00000331602.3

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

African (AFR) AF: 0.0477 AC: 1981 AN: 41548

American (AMR) AF: 0.0998 AC: 1526 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5174

South Asian (SAS) AF: 0.154 AC: 743 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1288 AN: 10592

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11433 AN: 67980

Other (OTH) AF: 0.120 AC: 253 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.71
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: rs112724859; hg19: chr3-53212212;