rs1557052362
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000033.4(ABCD1):c.442A>G(p.Asn148Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000033.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.442A>G | p.Asn148Asp | missense_variant | Exon 1 of 10 | ENST00000218104.6 | NP_000024.2 | |
ABCD1 | XM_047441916.1 | c.442A>G | p.Asn148Asp | missense_variant | Exon 1 of 11 | XP_047297872.1 | ||
ABCD1 | XM_047441917.1 | c.442A>G | p.Asn148Asp | missense_variant | Exon 1 of 8 | XP_047297873.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 26
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 26
ClinVar
Submissions by phenotype
Adrenoleukodystrophy Pathogenic:2
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This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 148 of the ABCD1 protein (p.Asn148Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 20800589; Invitae). ClinVar contains an entry for this variant (Variation ID: 862617). 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: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asn148 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7849723, 10190819, 10480364, 15811009; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at