rs385039

Variant names:

• chr1-2145970-A-G
• rs385039
• NM_002744.6:c.553-57A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-2145970-A-G
• chr1-2145970-A-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.553-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,461,188 control chromosomes in the GnomAD database, including 55,510 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 (4876 hom., cov: 32)
  • Exomes 𝑓: 0.27 (50634 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 17 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=-0.99).
• 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.553-57A>G		intron	N/A	NP_002735.3
	PRKCZ	NM_001242874.3		c.241-57A>G		intron	N/A	NP_001229803.1
	PRKCZ	NM_001350803.2		c.4-57A>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.553-57A>G		intron	N/A	ENSP00000367830.3
	PRKCZ	ENST00000400921.6	TSL:1	c.4-57A>G		intron	N/A	ENSP00000383712.2
	PRKCZ	ENST00000503672.1	TSL:1	n.156-57A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35854 AN: 152070 Hom.: 4873 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.274 AC: 358766 AN: 1309000 Hom.: 50634 AF XY: 0.275 AC XY: 181065 AN XY: 658572

African (AFR) AF: 0.0969 AC: 2908 AN: 30006

American (AMR) AF: 0.386 AC: 16785 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7476 AN: 25064

East Asian (EAS) AF: 0.184 AC: 7153 AN: 38918

South Asian (SAS) AF: 0.290 AC: 24022 AN: 82780

European-Finnish (FIN) AF: 0.305 AC: 16096 AN: 52764

Middle Eastern (MID) AF: 0.220 AC: 1206 AN: 5484

European-Non Finnish (NFE) AF: 0.276 AC: 269055 AN: 975316

Other (OTH) AF: 0.255 AC: 14065 AN: 55228

GnomAD4 genome AF: 0.236 AC: 35878 AN: 152188 Hom.: 4876 Cov.: 32 AF XY: 0.240 AC XY: 17871 AN XY: 74408

African (AFR) AF: 0.0998 AC: 4147 AN: 41550

American (AMR) AF: 0.332 AC: 5075 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1010 AN: 5176

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4818

European-Finnish (FIN) AF: 0.311 AC: 3291 AN: 10578

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

European-Non Finnish (NFE) AF: 0.281 AC: 19093 AN: 67988

Other (OTH) AF: 0.240 AC: 508 AN: 2116

Alfa AF: 0.265 Hom.: 7957

Bravo AF: 0.231

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.32
PhyloP100		-2.5
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: rs385039; hg19: chr1-2077409; COSMIC: COSV66065809; COSMIC: COSV66065809;