rs372774556
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000048.4(ASL):c.1045G>A(p.Val349Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V349V) has been classified as Likely benign.
Frequency
Consequence
NM_000048.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASL | NM_000048.4 | c.1045G>A | p.Val349Ile | missense_variant | 14/17 | ENST00000304874.14 | |
ASL | NM_001024943.2 | c.1045G>A | p.Val349Ile | missense_variant | 13/16 | ||
ASL | NM_001024944.2 | c.985G>A | p.Val329Ile | missense_variant | 12/15 | ||
ASL | NM_001024946.2 | c.967G>A | p.Val323Ile | missense_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASL | ENST00000304874.14 | c.1045G>A | p.Val349Ile | missense_variant | 14/17 | 1 | NM_000048.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250538Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135672
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461246Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 726936
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
Argininosuccinate lyase deficiency Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 349 of the ASL protein (p.Val349Ile). This variant is present in population databases (rs372774556, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ASL-related conditions. ClinVar contains an entry for this variant (Variation ID: 572182). 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 ASL 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.1045G>A (p.V349I) alteration is located in exon 14 (coding exon 13) of the ASL gene. This alteration results from a G to A substitution at nucleotide position 1045, causing the valine (V) at amino acid position 349 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at