19-56159677-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018337.4(ZNF444):c.460C>T(p.Arg154Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,520,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R154H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018337.4 missense
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF444 | NM_018337.4 | c.460C>T | p.Arg154Cys | missense_variant | Exon 5 of 5 | ENST00000337080.8 | NP_060807.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000227 AC: 31AN: 1368318Hom.: 0 Cov.: 31 AF XY: 0.0000178 AC XY: 12AN XY: 674212
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.460C>T (p.R154C) alteration is located in exon 5 (coding exon 3) of the ZNF444 gene. This alteration results from a C to T substitution at nucleotide position 460, causing the arginine (R) at amino acid position 154 to be replaced by a cysteine (C). 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