rs755359802
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3_ModeratePP5
The ENST00000623063.3(ADSL):c.581G>A(p.Arg194His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R194C) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000623063.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADSL | NM_000026.4 | c.581G>A | p.Arg194His | missense_variant | 5/13 | ENST00000623063.3 | NP_000017.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADSL | ENST00000623063.3 | c.581G>A | p.Arg194His | missense_variant | 5/13 | 1 | NM_000026.4 | ENSP00000485525 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251458Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Adenylosuccinate lyase deficiency Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 03, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 194 of the ADSL protein (p.Arg194His). This variant is present in population databases (rs755359802, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 529216). 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 ADSL 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. - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Sep 11, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at