chr19-46838541-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM1PP2BP4BS2
The NM_004069.6(AP2S1):c.335C>T(p.Thr112Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,062 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T112S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004069.6 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 | UniProt |
---|---|---|---|---|---|---|---|
AP2S1 | NM_004069.6 | c.335C>T | p.Thr112Met | missense_variant | 5/5 | ENST00000263270.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP2S1 | ENST00000263270.11 | c.335C>T | p.Thr112Met | missense_variant | 5/5 | 1 | NM_004069.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 14, 2023 | 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. Experimental studies have shown that this missense change affects AP2S1 function (PMID: 29325022). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 2150903). This variant has not been reported in the literature in individuals affected with AP2S1-related conditions. This variant is present in population databases (rs756038304, gnomAD 0.004%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 112 of the AP2S1 protein (p.Thr112Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at