rs777002501
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP2PP5
The NM_000017.4(ACADS):c.505A>C(p.Thr169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,798 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T169T) has been classified as Likely benign.
Frequency
Consequence
NM_000017.4 missense
Scores
Clinical Significance
Conservation
Publications
- short chain acyl-CoA dehydrogenase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.505A>C | p.Thr169Pro | missense_variant | Exon 5 of 10 | 1 | NM_000017.4 | ENSP00000242592.4 | ||
ACADS | ENST00000411593.2 | c.473-180A>C | intron_variant | Intron 4 of 9 | 2 | ENSP00000401045.2 | ||||
ENSG00000255946 | ENST00000724268.1 | n.305-7581T>G | intron_variant | Intron 1 of 1 | ||||||
ACADS | ENST00000539690.1 | n.*64A>C | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 151950Hom.: 1 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000438 AC: 11AN: 250984 AF XY: 0.0000516 show subpopulations
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461730Hom.: 1 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 727162 show subpopulations
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152068Hom.: 1 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74346 show subpopulations
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Pathogenic:2Uncertain:5
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 169 of the ACADS protein (p.Thr169Pro). This variant is present in population databases (rs777002501, gnomAD 0.04%). This missense change has been observed in individuals with short chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 16926354, 18676165, 22424739; Invitae). ClinVar contains an entry for this variant (Variation ID: 551228). 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 expected to disrupt ACADS protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. -
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at