rs180177255
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000030.3(AGXT):c.679_680+2delAAGT(p.Lys228fs) variant causes a frameshift, splice donor, splice region, intron change. The variant allele was found at a frequency of 0.00000205 in 1,461,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000030.3 frameshift, splice_donor, splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.679_680+2delAAGT | p.Lys228fs | frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant | 6/11 | ENST00000307503.4 | NP_000021.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.679_680+2delAAGT | p.Lys228fs | frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant | 6/11 | 1 | NM_000030.3 | ENSP00000302620.3 | ||
AGXT | ENST00000476698.1 | n.332+1012_332+1015delAAGT | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250856Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135676
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461118Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726872
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:4
Pathogenic, no assertion criteria provided | clinical testing | Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University | Aug 26, 2024 | Variant_type:truncating/MutationTaster:NONE/CADD:NONE/phyloP:NONE/phastCons:NONE/gnomAD_exome_EastAsian:NONE/ExAC_EastAsian:NONE/dbSNP:NONE - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 06, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 16, 2022 | - - |
Pathogenic, no assertion criteria provided | research | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 25, 2023 | This variant has been observed in individual(s) with hyperoxaluria (PMID: 11708860). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 679-(IVS6+2)delAAgt . ClinVar contains an entry for this variant (Variation ID: 204195). For these reasons, this variant has been classified as Pathogenic. This variant results in the deletion of part of exon 6 (c.679_680+2del) of the AGXT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AGXT are known to be pathogenic (PMID: 19479957). This variant is present in population databases (rs180177255, gnomAD 0.02%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at