chr1-2137467-G-T

Variant names:

• chr1-2137467-G-T
• rs3128296
• NM_002744.6:c.420+2120G>T

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+2120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,294 control chromosomes in the GnomAD database, including 63,803 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 0.91 (63803 hom., cov: 32)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 11 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.420+2120G>T		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+2120G>T		intron_variant	Intron 5 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139165 AN: 152176 Hom.: 63748 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.915 AC: 139279 AN: 152294 Hom.: 63803 Cov.: 32 AF XY: 0.920 AC XY: 68487 AN XY: 74460

African (AFR) AF: 0.959 AC: 39890 AN: 41574

American (AMR) AF: 0.941 AC: 14394 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 0.938 AC: 4845 AN: 5168

South Asian (SAS) AF: 0.906 AC: 4377 AN: 4830

European-Finnish (FIN) AF: 0.929 AC: 9861 AN: 10614

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59600 AN: 68016

Other (OTH) AF: 0.909 AC: 1922 AN: 2114

Alfa AF: 0.891 Hom.: 110503

Bravo AF: 0.918

Asia WGS AF: 0.918 AC: 3192 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	0.64
DANN	Benign	0.37
PhyloP100		-0.34
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: rs3128296; hg19: chr1-2068906;