X-15827336-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001272071.2(AP1S2):c.472G>A(p.Gly158Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,207,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 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. G158E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001272071.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP1S2 | NM_001272071.2 | c.472G>A | p.Gly158Arg | missense_variant | 6/6 | ENST00000672987.1 | |
AP1S2 | NM_003916.5 | c.463G>A | p.Gly155Arg | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP1S2 | ENST00000672987.1 | c.472G>A | p.Gly158Arg | missense_variant | 6/6 | NM_001272071.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111832Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34016
GnomAD4 exome AF: 0.0000137 AC: 15AN: 1095176Hom.: 0 Cov.: 28 AF XY: 0.00000831 AC XY: 3AN XY: 360876
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111832Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34016
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2020 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AP1S2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 155 of the AP1S2 protein (p.Gly155Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. 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