chr12-18699814-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033123.4(PLCZ1):c.1154G>A(p.Arg385Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,260 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 1 hom. )
Consequence
PLCZ1
NM_033123.4 missense
NM_033123.4 missense
Scores
5
8
Clinical Significance
Conservation
PhyloP100: 1.02
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCZ1 | NM_033123.4 | c.1154G>A | p.Arg385Gln | missense_variant | 10/15 | ENST00000266505.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCZ1 | ENST00000266505.12 | c.1154G>A | p.Arg385Gln | missense_variant | 10/15 | 1 | NM_033123.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152062Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250812Hom.: 1 AF XY: 0.0000368 AC XY: 5AN XY: 135726
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461198Hom.: 1 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726952
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152062Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74262
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spermatogenic failure 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 05, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;T;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
Polyphen
0.93, 0.94
.;P;P;.;.;.
Vest4
0.40, 0.35, 0.37
MutPred
0.47
.;.;Loss of MoRF binding (P = 0.025);.;.;.;
MVP
0.58
MPC
0.052
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -20
Find out detailed SpliceAI scores and Pangolin per-transcript scores at