1-2143812-A-G

Variant names:

• chr1-2143812-A-G
• rs2503706
• NM_002744.6:c.421-398A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002744.6(PRKCZ):​c.421-398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 161,426 control chromosomes in the GnomAD database, including 48,488 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (46088 hom., cov: 33)
  • Exomes 𝑓: 0.71 (2400 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 10 publications found

Genes affected

PRKCZ (HGNC:9412): (protein kinase C zeta) Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000271806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002744.6. 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
	PRKCZ	NM_002744.6	MANE Select	c.421-398A>G		intron	N/A	NP_002735.3
	PRKCZ	NM_001242874.3		c.109-398A>G		intron	N/A	NP_001229803.1
	PRKCZ	NM_001350803.2		c.-129-398A>G		intron	N/A	NP_001337732.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	ENST00000378567.8	TSL:1 MANE Select	c.421-398A>G		intron	N/A	ENSP00000367830.3
	PRKCZ	ENST00000400921.6	TSL:1	c.-129-398A>G		intron	N/A	ENSP00000383712.2
	ENSG00000271806	ENST00000606533.1	TSL:6	n.1468T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116922 AN: 152096 Hom.: 46016 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.714 AC: 6581 AN: 9212 Hom.: 2400 Cov.: 0 AF XY: 0.707 AC XY: 3328 AN XY: 4706

African (AFR) AF: 0.935 AC: 361 AN: 386

American (AMR) AF: 0.789 AC: 254 AN: 322

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 243 AN: 392

East Asian (EAS) AF: 0.960 AC: 526 AN: 548

South Asian (SAS) AF: 0.817 AC: 348 AN: 426

European-Finnish (FIN) AF: 0.658 AC: 192 AN: 292

Middle Eastern (MID) AF: 0.771 AC: 37 AN: 48

European-Non Finnish (NFE) AF: 0.675 AC: 4175 AN: 6184

Other (OTH) AF: 0.725 AC: 445 AN: 614

GnomAD4 genome AF: 0.769 AC: 117055 AN: 152214 Hom.: 46088 Cov.: 33 AF XY: 0.771 AC XY: 57385 AN XY: 74414

African (AFR) AF: 0.922 AC: 38338 AN: 41562

American (AMR) AF: 0.790 AC: 12090 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2119 AN: 3464

East Asian (EAS) AF: 0.947 AC: 4902 AN: 5178

South Asian (SAS) AF: 0.845 AC: 4072 AN: 4818

European-Finnish (FIN) AF: 0.670 AC: 7097 AN: 10590

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46089 AN: 67988

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.793 Hom.: 18817

Bravo AF: 0.784

Asia WGS AF: 0.882 AC: 3064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.22
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2503706; hg19: chr1-2075251;