rs1057516052
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000033.4(ABCD1):c.529C>T(p.Gln177Ter) variant causes a stop gained change involving the alteration of a non-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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q177Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000033.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.529C>T | p.Gln177Ter | stop_gained | 1/10 | ENST00000218104.6 | |
ABCD1 | XM_047441916.1 | c.529C>T | p.Gln177Ter | stop_gained | 1/11 | ||
ABCD1 | XM_047441917.1 | c.529C>T | p.Gln177Ter | stop_gained | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.529C>T | p.Gln177Ter | stop_gained | 1/10 | 1 | NM_000033.4 | P1 | |
ABCD1 | ENST00000370129.4 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 26
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 26
ClinVar
Submissions by phenotype
Adrenoleukodystrophy Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 25, 2021 | Variant summary: ABCD1 c.529C>T (p.Gln177X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 182774 control chromosomes (gnomAD). c.529C>T has been reported in the literature in individuals affected with Adrenoleukodystrophy (e.g. Lachtenmacher_2000, Asheuer_2005, Coll_2005, Lan_2011). These data indicate that the variant is likely to be associated with disease. Experimental evidence indicates that patient fibroblasts with the variant fail to express detectable levels of ALDP protein (e.g. Coll_2005). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 30, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with ABCD1-related conditions (PMID: 10737980, 24480483). ClinVar contains an entry for this variant (Variation ID: 369726). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln177*) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 08, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 29, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at