rs756742718
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001379286.1(ZNF423):c.3467C>T(p.Pro1156Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000066 in 1,604,970 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1156P) has been classified as Likely benign.
Frequency
Consequence
NM_001379286.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF423 | NM_001379286.1 | c.3467C>T | p.Pro1156Leu | missense_variant | 4/8 | ENST00000563137.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF423 | ENST00000563137.7 | c.3467C>T | p.Pro1156Leu | missense_variant | 4/8 | 5 | NM_001379286.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000133 AC: 32AN: 240812Hom.: 1 AF XY: 0.000145 AC XY: 19AN XY: 130708
GnomAD4 exome AF: 0.0000702 AC: 102AN: 1452728Hom.: 3 Cov.: 31 AF XY: 0.0000664 AC XY: 48AN XY: 722802
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2017 | The P1148L variant in the ZNF423 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P1148L variant is observed in 14/11518 (0.12%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1148L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P1148L as a variant of uncertain significance. - |
Nephronophthisis 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at