rs1557054745
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000033.4(ABCD1):c.1532G>A(p.Cys511Tyr) 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C511W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000033.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.1532G>A | p.Cys511Tyr | missense_variant | 6/10 | ENST00000218104.6 | |
LOC124905226 | XR_007068350.1 | n.1413C>T | non_coding_transcript_exon_variant | 1/2 | |||
ABCD1 | XM_047441916.1 | c.1832G>A | p.Cys611Tyr | missense_variant | 7/11 | ||
ABCD1 | XM_047441917.1 | c.1588G>A | p.Ala530Thr | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.1532G>A | p.Cys511Tyr | missense_variant | 6/10 | 1 | NM_000033.4 | P1 | |
PLXNB3-AS1 | ENST00000434284.1 | n.72-1557C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
ABCD1 | ENST00000443684.2 | n.535G>A | non_coding_transcript_exon_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 25
ClinVar
Submissions by phenotype
Adrenoleukodystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2021 | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 511 of the ABCD1 protein (p.Cys511Tyr). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 528344). This missense change has been observed in individual(s) with clinical features of ABCD1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 31, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at