chr12-18699832-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_033123.4(PLCZ1):c.1136T>C(p.Ile379Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,613,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
PLCZ1
NM_033123.4 missense
NM_033123.4 missense
Scores
2
7
4
Clinical Significance
Conservation
PhyloP100: 6.36
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000534 (78/1461284) while in subpopulation AMR AF= 0.000671 (30/44710). AF 95% confidence interval is 0.000483. There are 0 homozygotes in gnomad4_exome. There are 37 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCZ1 | NM_033123.4 | c.1136T>C | p.Ile379Thr | missense_variant | 10/15 | ENST00000266505.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCZ1 | ENST00000266505.12 | c.1136T>C | p.Ile379Thr | missense_variant | 10/15 | 1 | NM_033123.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 250852Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135698
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461284Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 726974
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2021 | The c.1136T>C (p.I379T) alteration is located in exon 10 (coding exon 9) of the PLCZ1 gene. This alteration results from a T to C substitution at nucleotide position 1136, causing the isoleucine (I) at amino acid position 379 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;T;T;T;D;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.92, 0.96
.;P;D;.;.;.
Vest4
0.77, 0.83, 0.79
MutPred
0.67
.;.;Gain of helix (P = 0.0117);.;.;.;
MVP
0.86
MPC
0.13
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at