rs868977355
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000033.4(ABCD1):c.238C>T(p.Arg80Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,804 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000033.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.238C>T | p.Arg80Trp | missense_variant | 1/10 | ENST00000218104.6 | NP_000024.2 | |
ABCD1 | XM_047441916.1 | c.238C>T | p.Arg80Trp | missense_variant | 1/11 | XP_047297872.1 | ||
ABCD1 | XM_047441917.1 | c.238C>T | p.Arg80Trp | missense_variant | 1/8 | XP_047297873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.238C>T | p.Arg80Trp | missense_variant | 1/10 | 1 | NM_000033.4 | ENSP00000218104.3 |
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD4 exome AF: 9.53e-7 AC: 1AN: 1049804Hom.: 0 Cov.: 32 AF XY: 0.00000300 AC XY: 1AN XY: 333062
GnomAD4 genome Cov.: 25
ClinVar
Submissions by phenotype
Adrenoleukodystrophy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 02, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 80 of the ABCD1 protein (p.Arg80Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with adrenoleukodystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 528336). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCD1 protein function. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at