chr19-46838490-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_004069.6(AP2S1):c.386C>T(p.Thr129Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T129T) has been classified as Likely benign.
Frequency
Consequence
NM_004069.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP2S1 | NM_004069.6 | c.386C>T | p.Thr129Met | missense_variant | 5/5 | ENST00000263270.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP2S1 | ENST00000263270.11 | c.386C>T | p.Thr129Met | missense_variant | 5/5 | 1 | NM_004069.6 | P4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461768Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727190
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 129 of the AP2S1 protein (p.Thr129Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AP2S1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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