chr14-31066278-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001128126.3(AP4S1):c.82C>T(p.Arg28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R28H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001128126.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4S1 | NM_001128126.3 | c.82C>T | p.Arg28Cys | missense_variant | 2/6 | ENST00000542754.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4S1 | ENST00000542754.7 | c.82C>T | p.Arg28Cys | missense_variant | 2/6 | 1 | NM_001128126.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251380Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135864
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461624Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727114
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74442
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | ClinVar contains an entry for this variant (Variation ID: 1694097). This variant has not been reported in the literature in individuals affected with AP4S1-related conditions. This variant is present in population databases (rs112987601, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 28 of the AP4S1 protein (p.Arg28Cys). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 12, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at