chr1-2150864-A-G

Variant names:

• chr1-2150864-A-G
• rs61729814
• NM_002744.6:c.762A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002744.6(PRKCZ):​c.762A>G​(p.Leu254Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: PRKCZ NM_002744.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.225
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-2150864-A-G is Benign according to our data. Variant chr1-2150864-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 764698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.225 with no splicing effect.
• BS2: High AC in GnomAd4 at 72 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.762A>G	p.Leu254Leu	synonymous	Exon 9 of 18	NP_002735.3
	PRKCZ	NM_001242874.3		c.450A>G	p.Leu150Leu	synonymous	Exon 6 of 15	NP_001229803.1	Q05513-3
	PRKCZ	NM_001350803.2		c.213A>G	p.Leu71Leu	synonymous	Exon 6 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.762A>G	p.Leu254Leu	synonymous	Exon 9 of 18	ENSP00000367830.3	Q05513-1
	PRKCZ	ENST00000400921.6	TSL:1	c.213A>G	p.Leu71Leu	synonymous	Exon 6 of 15	ENSP00000383712.2	Q05513-2
	PRKCZ	ENST00000503672.1	TSL:1	n.365A>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000955 AC: 24 AN: 251340 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000636 AC: 93 AN: 1461826 Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45 AN XY: 727214

African (AFR) AF: 0.00218 AC: 73 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.000298 AC: 18 AN: 60390

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74508

African (AFR) AF: 0.00171 AC: 71 AN: 41588

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000227 Hom.: 0

Bravo AF: 0.000487

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.7
DANN	Benign	0.61
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs61729814; hg19: chr1-2082303;