Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001353803.2(ZNF875):c.431A>T(p.Asp144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
Uncertain significance, criteria provided, single submitter
clinical testing
Ambry Genetics
Nov 14, 2023
The c.488A>T (p.D163V) alteration is located in exon 6 (coding exon 4) of the HKR1 gene. This alteration results from a A to T substitution at nucleotide position 488, causing the aspartic acid (D) at amino acid position 163 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -