3-53185605-GA-AG

Variant names:

• chr3-53185605-GA-AG
• NM_006254.4:c.890_891delGAinsAG
• PRKCD p.Arg297Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006254.4(PRKCD):​c.890_891delGAinsAG​(p.Arg297Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKCD NM_006254.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.890_891delGAinsAG	p.Arg297Lys	missense splice_region	N/A	NP_006245.2
	PRKCD	NM_001354676.2		c.947_948delGAinsAG	p.Arg316Lys	missense splice_region	N/A	NP_001341605.1
	PRKCD	NM_001354678.2		c.938_939delGAinsAG	p.Arg313Lys	missense splice_region	N/A	NP_001341607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.890_891delGAinsAG	p.Arg297Lys	missense splice_region	N/A	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.890_891delGAinsAG	p.Arg297Lys	missense splice_region	N/A	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.926_927delGAinsAG	p.Arg309Lys	missense splice_region	N/A	ENSP00000619524.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-53219621;