19-57779244-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_001077426.3(ZNF586):c.530T>G(p.Leu177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L177L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001077426.3 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 |
---|---|---|---|---|---|---|---|---|
ZNF586 | NM_017652.4 | c.657T>G | p.Ser219Ser | synonymous_variant | Exon 3 of 3 | ENST00000396154.7 | NP_060122.2 | |
ZNF586 | NM_001077426.3 | c.530T>G | p.Leu177Arg | missense_variant | Exon 2 of 2 | NP_001070894.1 | ||
ZNF586 | NM_001204814.2 | c.528T>G | p.Ser176Ser | synonymous_variant | Exon 4 of 4 | NP_001191743.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151932Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250628Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135822
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727242
GnomAD4 genome AF: 0.0000461 AC: 7AN: 151932Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74156
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at