rs1085307056
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM2PM5PP3PP5_Very_Strong
The NM_054012.4(ASS1):c.689G>C(p.Gly230Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G230R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_054012.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASS1 | NM_054012.4 | c.689G>C | p.Gly230Ala | missense_variant, splice_region_variant | 10/15 | ENST00000352480.10 | |
ASS1 | NM_000050.4 | c.689G>C | p.Gly230Ala | missense_variant, splice_region_variant | 11/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASS1 | ENST00000352480.10 | c.689G>C | p.Gly230Ala | missense_variant, splice_region_variant | 10/15 | 1 | NM_054012.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Citrullinemia type I Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 14, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Oct 02, 2021 | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic/likely pathogenic with supporting evidence (PMID: 23099195, PS1_P). It is not observed in the gnomAD v2.1.1 dataset (PM2). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.923, 3Cnet: 0.995, PP3). Patient is considered compatible with Snijders Citrullinemia (PP4_P).Therefore, this variant is classified as likley pathogenic according to the recommendation of ACMG/AMP guideline. - |
Likely pathogenic, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at