chr6-131573310-AT-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000045.4(ARG1):c.30del(p.Ile11LeufsTer21) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. I10I) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
ARG1
NM_000045.4 frameshift
NM_000045.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.62
Genes affected
ARG1 (HGNC:663): (arginase 1) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 73 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-131573310-AT-A is Pathogenic according to our data. Variant chr6-131573310-AT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 992369.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARG1 | NM_000045.4 | c.30del | p.Ile11LeufsTer21 | frameshift_variant | 1/8 | ENST00000368087.8 | |
ARG1 | NM_001244438.2 | c.30del | p.Ile11LeufsTer21 | frameshift_variant | 1/8 | ||
ARG1 | NM_001369020.1 | c.30del | p.Ile11LeufsTer21 | frameshift_variant | 1/6 | ||
ARG1 | NR_160934.1 | n.87del | non_coding_transcript_exon_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARG1 | ENST00000368087.8 | c.30del | p.Ile11LeufsTer21 | frameshift_variant | 1/8 | 1 | NM_000045.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Arginase deficiency Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare | Jun 16, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at