chr12-18701694-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_033123.4(PLCZ1):c.947G>A(p.Arg316His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,612,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R316C) has been classified 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCZ1 | NM_033123.4 | c.947G>A | p.Arg316His | missense_variant, splice_region_variant | 8/15 | ENST00000266505.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCZ1 | ENST00000266505.12 | c.947G>A | p.Arg316His | missense_variant, splice_region_variant | 8/15 | 1 | NM_033123.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000106 AC: 16AN: 151584Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250726Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135552
GnomAD4 exome AF: 0.000110 AC: 161AN: 1460452Hom.: 0 Cov.: 35 AF XY: 0.0000977 AC XY: 71AN XY: 726496
GnomAD4 genome ? AF: 0.0000989 AC: 15AN: 151698Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5AN XY: 74130
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at