1-2144121-T-G

Variant names:

• chr1-2144121-T-G
• rs427811
• NM_002744.6:c.421-89T>G

Variant summary

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

The NM_002744.6(PRKCZ):​c.421-89T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,479,954 control chromosomes in the GnomAD database, including 55,194 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 0.24 (4838 hom., cov: 33)
  • Exomes 𝑓: 0.27 (50356 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 14 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]

ENSG00000271806 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	NM_002744.6	MANE Select	c.421-89T>G		intron	N/A	NP_002735.3
	PRKCZ	NM_001242874.3		c.109-89T>G		intron	N/A	NP_001229803.1	Q05513-3
	PRKCZ	NM_001350803.2		c.-129-89T>G		intron	N/A	NP_001337732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	ENST00000378567.8	TSL:1 MANE Select	c.421-89T>G		intron	N/A	ENSP00000367830.3	Q05513-1
	PRKCZ	ENST00000400921.6	TSL:1	c.-129-89T>G		intron	N/A	ENSP00000383712.2	Q05513-2
	PRKCZ	ENST00000965048.1		c.421-89T>G		intron	N/A	ENSP00000635107.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35803 AN: 151994 Hom.: 4835 Cov.: 33

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.272 AC: 360517 AN: 1327842 Hom.: 50356 Cov.: 24 AF XY: 0.273 AC XY: 176733 AN XY: 647516

African (AFR) AF: 0.0963 AC: 2869 AN: 29806

American (AMR) AF: 0.376 AC: 11300 AN: 30028

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 6511 AN: 21872

East Asian (EAS) AF: 0.184 AC: 6313 AN: 34288

South Asian (SAS) AF: 0.291 AC: 21034 AN: 72314

European-Finnish (FIN) AF: 0.306 AC: 14262 AN: 46674

Middle Eastern (MID) AF: 0.225 AC: 1027 AN: 4566

European-Non Finnish (NFE) AF: 0.274 AC: 283418 AN: 1033748

Other (OTH) AF: 0.253 AC: 13783 AN: 54546

GnomAD4 genome AF: 0.236 AC: 35827 AN: 152112 Hom.: 4838 Cov.: 33 AF XY: 0.240 AC XY: 17839 AN XY: 74356

African (AFR) AF: 0.0996 AC: 4139 AN: 41544

American (AMR) AF: 0.332 AC: 5073 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1021 AN: 5168

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4828

European-Finnish (FIN) AF: 0.310 AC: 3276 AN: 10562

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19055 AN: 67932

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.262 Hom.: 898

Bravo AF: 0.232

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.44
PhyloP100		-1.6
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: rs427811; hg19: chr1-2075560; COSMIC: COSV66071058; COSMIC: COSV66071058;