3-53174901-T-C

Variant names:

• chr3-53174901-T-C
• rs3821689
• NM_006254.4:c.-19-3503T>C

Variant summary

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

The NM_006254.4(PRKCD):​c.-19-3503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,060 control chromosomes in the GnomAD database, including 27,911 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 0.60 (27911 hom., cov: 33)
• Consequence: PRKCD NM_006254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.-19-3503T>C		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.-19-3503T>C		intron_variant	Intron 2 of 18	1	NM_006254.4	ENSP00000331602.3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90495 AN: 151942 Hom.: 27901 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.595 AC: 90540 AN: 152060 Hom.: 27911 Cov.: 33 AF XY: 0.600 AC XY: 44597 AN XY: 74356

African (AFR) AF: 0.431 AC: 17883 AN: 41452

American (AMR) AF: 0.648 AC: 9911 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2486 AN: 3466

East Asian (EAS) AF: 0.747 AC: 3863 AN: 5170

South Asian (SAS) AF: 0.589 AC: 2843 AN: 4826

European-Finnish (FIN) AF: 0.748 AC: 7924 AN: 10588

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43507 AN: 67958

Other (OTH) AF: 0.616 AC: 1299 AN: 2108

Alfa AF: 0.608 Hom.: 4663

Bravo AF: 0.585

Asia WGS AF: 0.636 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		0.71
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: rs3821689; hg19: chr3-53208917;