rs142352833

Variant names:

• chr1-2173988-C-T
• rs142352833
• NM_002744.6:c.1377C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2173988-C-T
• chr1-2173988-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002744.6(PRKCZ):​c.1377C>T​(p.Asp459Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,612,534 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (9 hom.)
• Consequence: PRKCZ NM_002744.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86
• Publications: 3 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-2173988-C-T is Benign according to our data. Variant chr1-2173988-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 184 AD gene.

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.1377C>T	p.Asp459Asp	synonymous	Exon 14 of 18	NP_002735.3
	PRKCZ	NM_001242874.3		c.1065C>T	p.Asp355Asp	synonymous	Exon 11 of 15	NP_001229803.1	Q05513-3
	PRKCZ	NM_001350803.2		c.852C>T	p.Asp284Asp	synonymous	Exon 11 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.1377C>T	p.Asp459Asp	synonymous	Exon 14 of 18	ENSP00000367830.3	Q05513-1
	PRKCZ	ENST00000400921.6	TSL:1	c.828C>T	p.Asp276Asp	synonymous	Exon 11 of 15	ENSP00000383712.2	Q05513-2
	PRKCZ	ENST00000965048.1		c.1650C>T	p.Asp550Asp	synonymous	Exon 15 of 19	ENSP00000635107.1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152234 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00102 AC: 254 AN: 249314 AF XY: 0.000972

Gnomad AFR exome AF: 0.000618

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00217 AC: 3168 AN: 1460182 Hom.: 9 Cov.: 30 AF XY: 0.00205 AC XY: 1488 AN XY: 726298

African (AFR) AF: 0.000689 AC: 23 AN: 33404

American (AMR) AF: 0.000202 AC: 9 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.000466 AC: 40 AN: 85894

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53378

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5758

European-Non Finnish (NFE) AF: 0.00268 AC: 2979 AN: 1111254

Other (OTH) AF: 0.00167 AC: 101 AN: 60330

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152352 Hom.: 1 Cov.: 32 AF XY: 0.000873 AC XY: 65 AN XY: 74498

African (AFR) AF: 0.000601 AC: 25 AN: 41586

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.00129

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00186

EpiControl AF: 0.00196

ClinVar

ClinVar submissions

Significance: Likely 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	-0.55
CADD	Benign	7.9
DANN	Benign	0.56
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs142352833; hg19: chr1-2105427; COSMIC: COSV66067505;