chr12-18688792-A-C

Position:

• chr12-18688792-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033123.4(PLCZ1):​c.1462-574T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,762 control chromosomes in the GnomAD database, including 12,309 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 0.39 (12309 hom., cov: 31)
• Consequence: PLCZ1 NM_033123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

Genes affected

PLCZ1 (HGNC:19218): (phospholipase C zeta 1) The protein encoded by this gene is a member of the phosphoinositide-specific phospholipase C family. Members in this family, classified into six isotypes that are tissue- and organ-specific, hydrolyze phosphatidylinositol 4,5-bisphosphate just before the phosphate group to yield diacylglycerol and inositol 1,4,5-trisphosphate. This protein localizes to the acrosome in spermatozoa and elicits Ca(2+) oscillations and egg activation during fertilization that leads to early embryonic development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

PIK3C2G (HGNC:8973): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PLCZ1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCZ1	NM_033123.4	c.1462-574T>G		intron_variant		ENST00000266505.12	NP_149114.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCZ1	ENST00000266505.12	c.1462-574T>G		intron_variant		1	NM_033123.4	ENSP00000266505.7
PLCZ1	ENST00000648272.1	c.1585-574T>G		intron_variant				ENSP00000497636.1
PLCZ1	ENST00000539875.5	c.883-574T>G		intron_variant		1		ENSP00000445026.1
PLCZ1	ENST00000318197.10	n.*1327-574T>G		intron_variant		1		ENSP00000326397.6

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59411 AN: 151642 Hom.: 12287 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59484 AN: 151762 Hom.: 12309 Cov.: 31 AF XY: 0.393 AC XY: 29172 AN XY: 74136

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.394

Alfa AF: 0.369 Hom.: 2604

Bravo AF: 0.410

Asia WGS AF: 0.366 AC: 1266 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7969692; hg19: chr12-18841726;