1-2138882-T-C

Variant names:

• chr1-2138882-T-C
• rs411021
• NM_002744.6:c.420+3535T>C

Variant summary

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

The NM_002744.6(PRKCZ):​c.420+3535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,116 control chromosomes in the GnomAD database, including 45,102 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 0.76 (45102 hom., cov: 32)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.420+3535T>C		intron_variant	Intron 5 of 17	ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.420+3535T>C		intron_variant	Intron 5 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116207 AN: 151998 Hom.: 45064 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.765 AC: 116300 AN: 152116 Hom.: 45102 Cov.: 32 AF XY: 0.760 AC XY: 56532 AN XY: 74362

African (AFR) AF: 0.901 AC: 37399 AN: 41524

American (AMR) AF: 0.668 AC: 10208 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2403 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4166 AN: 5178

South Asian (SAS) AF: 0.715 AC: 3452 AN: 4826

European-Finnish (FIN) AF: 0.688 AC: 7265 AN: 10552

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48897 AN: 67972

Other (OTH) AF: 0.760 AC: 1602 AN: 2108

Alfa AF: 0.634 Hom.: 1915

Bravo AF: 0.769

Asia WGS AF: 0.801 AC: 2789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.14
PhyloP100		-1.5
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: rs411021; hg19: chr1-2070321;