chr1-2172067-C-G

Variant names:

• chr1-2172067-C-G
• rs2280272
• NM_002744.6:c.1074C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_002744.6(PRKCZ):​c.1074C>G​(p.Ala358Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,609,038 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (152 hom.)
• Consequence: PRKCZ NM_002744.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00
• Publications: 8 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-2172067-C-G is Benign according to our data. Variant chr1-2172067-C-G is described in ClinVar as Benign. ClinVar VariationId is 718957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0753 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.1074C>G	p.Ala358Ala	synonymous	Exon 12 of 18	NP_002735.3
	PRKCZ	NM_001242874.3		c.762C>G	p.Ala254Ala	synonymous	Exon 9 of 15	NP_001229803.1	Q05513-3
	PRKCZ	NM_001350803.2		c.549C>G	p.Ala183Ala	synonymous	Exon 9 of 15	NP_001337732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	ENST00000378567.8	TSL:1 MANE Select	c.1074C>G	p.Ala358Ala	synonymous	Exon 12 of 18	ENSP00000367830.3	Q05513-1
	PRKCZ	ENST00000400921.6	TSL:1	c.525C>G	p.Ala175Ala	synonymous	Exon 9 of 15	ENSP00000383712.2	Q05513-2
	PRKCZ	ENST00000965048.1		c.1347C>G	p.Ala449Ala	synonymous	Exon 13 of 19	ENSP00000635107.1

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 587 AN: 152216 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00764 AC: 1881 AN: 246284 AF XY: 0.00717

Gnomad AFR exome AF: 0.000805

Gnomad AMR exome AF: 0.000322

Gnomad ASJ exome AF: 0.00167

Gnomad EAS exome AF: 0.0830

Gnomad FIN exome AF: 0.00451

Gnomad NFE exome AF: 0.000568

Gnomad OTH exome AF: 0.00584

GnomAD4 exome AF: 0.00325 AC: 4732 AN: 1456704 Hom.: 152 Cov.: 32 AF XY: 0.00326 AC XY: 2359 AN XY: 724382

African (AFR) AF: 0.000299 AC: 10 AN: 33390

American (AMR) AF: 0.000293 AC: 13 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 54 AN: 25684

East Asian (EAS) AF: 0.0821 AC: 3255 AN: 39662

South Asian (SAS) AF: 0.00427 AC: 365 AN: 85496

European-Finnish (FIN) AF: 0.00431 AC: 227 AN: 52624

Middle Eastern (MID) AF: 0.00192 AC: 11 AN: 5738

European-Non Finnish (NFE) AF: 0.000370 AC: 411 AN: 1109520

Other (OTH) AF: 0.00641 AC: 386 AN: 60208

GnomAD4 genome AF: 0.00382 AC: 582 AN: 152334 Hom.: 18 Cov.: 32 AF XY: 0.00426 AC XY: 317 AN XY: 74486

African (AFR) AF: 0.000793 AC: 33 AN: 41590

American (AMR) AF: 0.000457 AC: 7 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0817 AC: 423 AN: 5178

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68026

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00405

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.028
DANN	Benign	0.45
PhyloP100		-2.0
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2280272; hg19: chr1-2103506; COSMIC: COSV66067651;