19-53408424-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000396408.8(ZNF765):c.869G>A(p.Arg290His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. R290C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000396408.8 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF765 | NM_001040185.3 | c.869G>A | p.Arg290His | missense_variant | 4/4 | ENST00000396408.8 | NP_001035275.1 | |
ZNF765 | NM_001350495.2 | c.710G>A | p.Arg237His | missense_variant | 3/3 | NP_001337424.1 | ||
ZNF765-ZNF761 | NM_001350496.2 | c.-1345+6233G>A | intron_variant | NP_001337425.1 | ||||
ZNF765 | NR_146721.2 | n.260+6233G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF765 | ENST00000396408.8 | c.869G>A | p.Arg290His | missense_variant | 4/4 | 1 | NM_001040185.3 | ENSP00000379689.3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151850Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251204Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135860
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461806Hom.: 0 Cov.: 86 AF XY: 0.0000234 AC XY: 17AN XY: 727194
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151850Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74170
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.869G>A (p.R290H) alteration is located in exon 4 (coding exon 3) of the ZNF765 gene. This alteration results from a G to A substitution at nucleotide position 869, causing the arginine (R) at amino acid position 290 to be replaced by a histidine (H). 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