rs1554725061
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_054012.4(ASS1):āc.1025A>Cā(p.Gln342Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q342R) has been classified as Uncertain significance.
Frequency
Consequence
NM_054012.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASS1 | NM_054012.4 | c.1025A>C | p.Gln342Pro | missense_variant | 13/15 | ENST00000352480.10 | |
ASS1 | NM_000050.4 | c.1025A>C | p.Gln342Pro | missense_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASS1 | ENST00000352480.10 | c.1025A>C | p.Gln342Pro | missense_variant | 13/15 | 1 | NM_054012.4 | P1 | |
ASS1 | ENST00000372393.7 | c.1025A>C | p.Gln342Pro | missense_variant | 14/16 | 5 | P1 | ||
ASS1 | ENST00000372394.5 | c.1025A>C | p.Gln342Pro | missense_variant | 14/16 | 2 | P1 | ||
ASS1 | ENST00000372386.6 | n.296A>C | non_coding_transcript_exon_variant | 4/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Citrullinemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 03, 2022 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 342 of the ASS1 protein (p.Gln342Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ASS1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at