12-18683278-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_033123.4(PLCZ1):c.1788G>A(p.Glu596Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,584 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 (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
PLCZ1
NM_033123.4 synonymous
NM_033123.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.18
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 12-18683278-C-T is Benign according to our data. Variant chr12-18683278-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033794.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.18 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCZ1 | NM_033123.4 | c.1788G>A | p.Glu596Glu | synonymous_variant | 15/15 | ENST00000266505.12 | NP_149114.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCZ1 | ENST00000266505.12 | c.1788G>A | p.Glu596Glu | synonymous_variant | 15/15 | 1 | NM_033123.4 | ENSP00000266505.7 | ||
PLCZ1 | ENST00000648272.1 | c.1911G>A | p.Glu637Glu | synonymous_variant | 14/14 | ENSP00000497636.1 | ||||
PLCZ1 | ENST00000539875.5 | c.1209G>A | p.Glu403Glu | synonymous_variant | 11/11 | 1 | ENSP00000445026.1 | |||
PLCZ1 | ENST00000318197.10 | n.*1653G>A | non_coding_transcript_exon_variant | 15/15 | 1 | ENSP00000326397.6 | ||||
PLCZ1 | ENST00000318197.10 | n.*1653G>A | 3_prime_UTR_variant | 15/15 | 1 | ENSP00000326397.6 |
Frequencies
GnomAD3 genomes AF: 0.0000527 AC: 8AN: 151932Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250388Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135312
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460534Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726610
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74322
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PLCZ1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at