NM_002744.6:c.1668C>G

Variant names:

• chr1-2184675-C-G
• rs56402864
• NM_002744.6:c.1668C>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.1668C>G​(p.Pro556Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,726 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (5 hom.)
• Consequence: PRKCZ NM_002744.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.79
• Publications: 1 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]

FAAP20 (HGNC:26428): (FA core complex associated protein 20) Enables K63-linked polyubiquitin modification-dependent protein binding activity and ubiquitin-dependent protein binding activity. Involved in interstrand cross-link repair and translesion synthesis. Located in cell junction; chromosome; and nuclear body. Part of Fanconi anaemia nuclear complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-2184675-C-G is Benign according to our data. Variant chr1-2184675-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1711203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BS2: High AC in GnomAd4 at 226 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.1668C>G	p.Pro556Pro	synonymous	Exon 17 of 18	NP_002735.3
	PRKCZ	NM_001242874.3		c.1356C>G	p.Pro452Pro	synonymous	Exon 14 of 15	NP_001229803.1	Q05513-3
	PRKCZ	NM_001350803.2		c.1143C>G	p.Pro381Pro	synonymous	Exon 14 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.1668C>G	p.Pro556Pro	synonymous	Exon 17 of 18	ENSP00000367830.3	Q05513-1
	PRKCZ	ENST00000400921.6	TSL:1	c.1119C>G	p.Pro373Pro	synonymous	Exon 14 of 15	ENSP00000383712.2	Q05513-2
	FAAP20	ENST00000428120.5	TSL:1	n.*1536G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000405430.1	H7C2E6

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 226 AN: 152220 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00135 AC: 337 AN: 250146 AF XY: 0.00145

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00255

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00166 AC: 2423 AN: 1461388 Hom.: 5 Cov.: 31 AF XY: 0.00170 AC XY: 1234 AN XY: 726964

African (AFR) AF: 0.000149 AC: 5 AN: 33468

American (AMR) AF: 0.000627 AC: 28 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86194

European-Finnish (FIN) AF: 0.00216 AC: 115 AN: 53254

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00191 AC: 2129 AN: 1111832

Other (OTH) AF: 0.00146 AC: 88 AN: 60384

GnomAD4 genome AF: 0.00148 AC: 226 AN: 152338 Hom.: 1 Cov.: 33 AF XY: 0.00152 AC XY: 113 AN XY: 74494

African (AFR) AF: 0.000192 AC: 8 AN: 41592

American (AMR) AF: 0.00170 AC: 26 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00234 AC: 159 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00205 Hom.: 1

Bravo AF: 0.00146

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00178

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	0.088
DANN	Benign	0.80
PhyloP100		-2.8
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs56402864; hg19: chr1-2116114;