1-2137733-C-T

Variant names:

• chr1-2137733-C-T
• rs425277
• NM_002744.6:c.420+2386C>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+2386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,138 control chromosomes in the GnomAD database, including 4,775 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 0.23 (4775 hom., cov: 32)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 54 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.420+2386C>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+2386C>T		intron_variant	Intron 5 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35432 AN: 152020 Hom.: 4770 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.233 AC: 35455 AN: 152138 Hom.: 4775 Cov.: 32 AF XY: 0.237 AC XY: 17655 AN XY: 74362

African (AFR) AF: 0.0974 AC: 4047 AN: 41542

American (AMR) AF: 0.329 AC: 5024 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.191 AC: 988 AN: 5166

South Asian (SAS) AF: 0.280 AC: 1353 AN: 4824

European-Finnish (FIN) AF: 0.307 AC: 3238 AN: 10556

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18992 AN: 67974

Other (OTH) AF: 0.235 AC: 497 AN: 2112

Alfa AF: 0.263 Hom.: 17891

Bravo AF: 0.229

Asia WGS AF: 0.195 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.35
PhyloP100		-1.9
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: rs425277; hg19: chr1-2069172;