rs566369623
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000369569.6(AP4B1):āc.215T>Cā(p.Met72Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,238 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M72I) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000369569.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP4B1 | NM_001253852.3 | c.215T>C | p.Met72Thr | missense_variant | 2/10 | ENST00000369569.6 | NP_001240781.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP4B1 | ENST00000369569.6 | c.215T>C | p.Met72Thr | missense_variant | 2/10 | 1 | NM_001253852.3 | ENSP00000358582 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251492Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135920
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727246
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74494
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 47 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 04, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 72 of the AP4B1 protein (p.Met72Thr). This variant is present in population databases (rs566369623, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575639). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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