8-107251893-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001146.5(ANGPT1):c.1459C>T(p.Arg487Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R487H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001146.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPT1 | NM_001146.5 | c.1459C>T | p.Arg487Cys | missense_variant | 9/9 | ENST00000517746.6 | |
ANGPT1 | NM_001199859.3 | c.1456C>T | p.Arg486Cys | missense_variant | 9/9 | ||
ANGPT1 | NM_001314051.2 | c.859C>T | p.Arg287Cys | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPT1 | ENST00000517746.6 | c.1459C>T | p.Arg487Cys | missense_variant | 9/9 | 1 | NM_001146.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251348Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461666Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727124
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 04, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 487 of the ANGPT1 protein (p.Arg487Cys). This variant is present in population databases (rs771962601, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ANGPT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at