rs200608977
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_004035.7(ACOX1):c.1418C>T(p.Thr473Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,614,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T473T) has been classified as Likely benign.
Frequency
Consequence
NM_004035.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACOX1 | NM_004035.7 | c.1418C>T | p.Thr473Ile | missense_variant | 10/14 | ENST00000293217.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACOX1 | ENST00000293217.10 | c.1418C>T | p.Thr473Ile | missense_variant | 10/14 | 1 | NM_004035.7 | A1 | |
ACOX1 | ENST00000301608.9 | c.1418C>T | p.Thr473Ile | missense_variant | 10/14 | 1 | P3 | ||
ACOX1 | ENST00000572047.5 | c.*1376C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/14 | 2 | ||||
ACOX1 | ENST00000573078.5 | c.*907C>T | 3_prime_UTR_variant, NMD_transcript_variant | 11/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000316 AC: 48AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 42AN: 251472Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135906
GnomAD4 exome AF: 0.000259 AC: 379AN: 1461894Hom.: 1 Cov.: 32 AF XY: 0.000250 AC XY: 182AN XY: 727248
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74420
ClinVar
Submissions by phenotype
Acyl-CoA oxidase deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 15, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 473 of the ACOX1 protein (p.Thr473Ile). This variant is present in population databases (rs200608977, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ACOX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 445693). 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) performed at Invitae indicates that this missense variant is not expected to disrupt ACOX1 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. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2024 | The c.1418C>T (p.T473I) alteration is located in exon 10 (coding exon 10) of the ACOX1 gene. This alteration results from a C to T substitution at nucleotide position 1418, causing the threonine (T) at amino acid position 473 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 20, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at