rs377115507

Variant names:

• chr3-53178479-C-A
• rs377115507
• NM_006254.4:c.57C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-53178479-C-A
• chr3-53178479-C-G
• chr3-53178479-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006254.4(PRKCD):​c.57C>A​(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A19A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.99
• 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):

• systemic lupus erythematosus

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-53178479-C-A is Benign according to our data. Variant chr3-53178479-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1622034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	NM_006254.4	MANE Select	c.57C>A	p.Ala19Ala	synonymous	Exon 3 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.114C>A	p.Ala38Ala	synonymous	Exon 2 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.105C>A	p.Ala35Ala	synonymous	Exon 2 of 18	NP_001341607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.57C>A	p.Ala19Ala	synonymous	Exon 3 of 19	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.57C>A	p.Ala19Ala	synonymous	Exon 2 of 18	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.57C>A	p.Ala19Ala	synonymous	Exon 2 of 18	ENSP00000619524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460788 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726682

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.18
DANN	Benign	0.50
PhyloP100		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs377115507; hg19: chr3-53212495; COSMIC: COSV100388010;