chr3-53189986-T-G

Variant names:

• chr3-53189986-T-G
• rs900495
• NM_006254.4:c.1857T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006254.4(PRKCD):​c.1857T>G​(p.Pro619Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P619P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675
• Publications: 19 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.675 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	NM_006254.4	MANE Select	c.1857T>G	p.Pro619Pro	synonymous	Exon 18 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.1914T>G	p.Pro638Pro	synonymous	Exon 17 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.1905T>G	p.Pro635Pro	synonymous	Exon 17 of 18	NP_001341607.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.1857T>G	p.Pro619Pro	synonymous	Exon 18 of 19	ENSP00000331602.3
	PRKCD	ENST00000394729.6	TSL:1	c.1857T>G	p.Pro619Pro	synonymous	Exon 17 of 18	ENSP00000378217.2
	PRKCD	ENST00000650739.1		c.1857T>G	p.Pro619Pro	synonymous	Exon 18 of 19	ENSP00000498623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		-0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs900495; hg19: chr3-53224002;