1-2104245-C-T

Variant names:

• chr1-2104245-C-T
• rs10910030
• NM_002744.6:c.335-31017C>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.335-31017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,718 control chromosomes in the GnomAD database, including 24,117 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 0.56 (24117 hom., cov: 31)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 9 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]

ENSG00000308181 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.335-31017C>T		intron_variant	Intron 4 of 17	ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.335-31017C>T		intron_variant	Intron 4 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84397 AN: 151598 Hom.: 24124 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.556 AC: 84418 AN: 151718 Hom.: 24117 Cov.: 31 AF XY: 0.560 AC XY: 41494 AN XY: 74146

African (AFR) AF: 0.425 AC: 17581 AN: 41344

American (AMR) AF: 0.543 AC: 8269 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3452 AN: 5120

South Asian (SAS) AF: 0.611 AC: 2933 AN: 4804

European-Finnish (FIN) AF: 0.632 AC: 6665 AN: 10550

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41243 AN: 67884

Other (OTH) AF: 0.575 AC: 1213 AN: 2108

Alfa AF: 0.584 Hom.: 59824

Bravo AF: 0.545

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.46
PhyloP100		0.10
PromoterAI		0.0036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs10910030; hg19: chr1-2035684;