chr3-53185643-G-C

Variant names:

• chr3-53185643-G-C
• rs773144753
• NM_006254.4:c.928G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006254.4(PRKCD):​c.928G>C​(p.Val310Leu) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V310I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRKCD NM_006254.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13363463).

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.928G>C	p.Val310Leu	missense	Exon 11 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.985G>C	p.Val329Leu	missense	Exon 10 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.976G>C	p.Val326Leu	missense	Exon 10 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.928G>C	p.Val310Leu	missense	Exon 11 of 19	ENSP00000331602.3
	PRKCD	ENST00000394729.6	TSL:1	c.928G>C	p.Val310Leu	missense	Exon 10 of 18	ENSP00000378217.2
	PRKCD	ENST00000650739.1		c.928G>C	p.Val310Leu	missense	Exon 11 of 19	ENSP00000498623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.61
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.025
Sift	Benign	0.48	T
Sift4G	Benign	0.77	T
Polyphen		0.011	B
Vest4		0.12
MutPred		0.33		Gain of glycosylation at Y313 (P = 0.0099)
MVP		0.65
MPC		0.80
ClinPred		0.14	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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: rs773144753; hg19: chr3-53219659;