rs7513222

Variant names:

• chr1-2096462-G-A
• rs7513222
• NM_002744.6:c.334+36871G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2096462-G-A
• chr1-2096462-G-C
• chr1-2096462-G-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.334+36871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,958 control chromosomes in the GnomAD database, including 8,400 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 0.30 (8400 hom., cov: 29)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997
• Publications: 12 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 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.334+36871G>A		intron	N/A	NP_002735.3
	PRKCZ	NM_001242874.3		c.22+22187G>A		intron	N/A	NP_001229803.1
	PRKCZ	NM_001350803.2		c.-216+22533G>A		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.334+36871G>A		intron	N/A	ENSP00000367830.3
	PRKCZ	ENST00000400921.6	TSL:1	c.-216+22533G>A		intron	N/A	ENSP00000383712.2
	PRKCZ	ENST00000461106.6	TSL:2	c.22+22187G>A		intron	N/A	ENSP00000426412.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46288 AN: 151838 Hom.: 8394 Cov.: 29

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.305 AC: 46306 AN: 151958 Hom.: 8400 Cov.: 29 AF XY: 0.319 AC XY: 23690 AN XY: 74262

African (AFR) AF: 0.123 AC: 5122 AN: 41486

American (AMR) AF: 0.408 AC: 6240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3178 AN: 5132

South Asian (SAS) AF: 0.476 AC: 2292 AN: 4812

European-Finnish (FIN) AF: 0.457 AC: 4825 AN: 10550

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22256 AN: 67914

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.307 Hom.: 18252

Bravo AF: 0.294

Asia WGS AF: 0.522 AC: 1813 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	0.039
DANN	Benign	0.64
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7513222; hg19: chr1-2027901;