16-4752476-C-T
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_021646.4(ZNF500):c.1343G>A(p.Arg448Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,545,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R448W) has been classified as Uncertain significance.
Frequency
Consequence
NM_021646.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF500 | NM_021646.4 | c.1343G>A | p.Arg448Gln | missense_variant | Exon 6 of 6 | ENST00000219478.11 | NP_067678.1 | |
ZNF500 | XM_005255243.5 | c.992G>A | p.Arg331Gln | missense_variant | Exon 5 of 5 | XP_005255300.1 | ||
ZNF500 | NM_001303450.2 | c.1297+46G>A | intron_variant | Intron 6 of 6 | NP_001290379.1 | |||
ZNF500 | XM_011522453.3 | c.1297+46G>A | intron_variant | Intron 6 of 6 | XP_011520755.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 151992Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.000113 AC: 17AN: 149898 AF XY: 0.000111 show subpopulations
GnomAD4 exome AF: 0.000135 AC: 188AN: 1393118Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 91AN XY: 688322 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000151 AC: 23AN: 152110Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9AN XY: 74374 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1343G>A (p.R448Q) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a G to A substitution at nucleotide position 1343, causing the arginine (R) at amino acid position 448 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