chr12-18699796-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033123.4(PLCZ1):c.1172G>A(p.Arg391Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033123.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCZ1 | NM_033123.4 | c.1172G>A | p.Arg391Gln | missense_variant, splice_region_variant | 10/15 | ENST00000266505.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCZ1 | ENST00000266505.12 | c.1172G>A | p.Arg391Gln | missense_variant, splice_region_variant | 10/15 | 1 | NM_033123.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152038Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250716Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135738
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460840Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726802
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152038Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.1172G>A (p.R391Q) alteration is located in exon 10 (coding exon 9) of the PLCZ1 gene. This alteration results from a G to A substitution at nucleotide position 1172, causing the arginine (R) at amino acid position 391 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at