rs182290450

Variant names:

• chr3-53189254-C-A
• rs182290450
• NM_006254.4:c.1743+8C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-53189254-C-A
• chr3-53189254-C-G
• chr3-53189254-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006254.4(PRKCD):​c.1743+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,409,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRKCD NM_006254.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003849
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.404
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.1743+8C>A		splice_region_variant, intron_variant	Intron 17 of 18	ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8	c.1743+8C>A		splice_region_variant, intron_variant	Intron 17 of 18	1	NM_006254.4	ENSP00000331602.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409800 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 701708

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32208

American (AMR) AF: 0.00 AC: 0 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24946

East Asian (EAS) AF: 0.00 AC: 0 AN: 38902

South Asian (SAS) AF: 0.00 AC: 0 AN: 84282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071884

Other (OTH) AF: 0.00 AC: 0 AN: 58134

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.33
PhyloP100		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0040
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: rs182290450; hg19: chr3-53223270;