rs746419489
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The ENST00000370646.9(HOGA1):c.117C>A(p.Tyr39Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,468 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y39Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000370646.9 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HOGA1 | NM_138413.4 | c.117C>A | p.Tyr39Ter | stop_gained | 1/7 | ENST00000370646.9 | NP_612422.2 | |
HOGA1 | NM_001134670.2 | c.117C>A | p.Tyr39Ter | stop_gained | 1/3 | NP_001128142.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOGA1 | ENST00000370646.9 | c.117C>A | p.Tyr39Ter | stop_gained | 1/7 | 1 | NM_138413.4 | ENSP00000359680 | P1 | |
HOGA1 | ENST00000370647.8 | c.117C>A | p.Tyr39Ter | stop_gained | 1/3 | 1 | ENSP00000359681 | |||
HOGA1 | ENST00000465608.1 | n.498C>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249684Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135074
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727004
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74278
ClinVar
Submissions by phenotype
Primary hyperoxaluria type 3 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 24, 2020 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 23, 2023 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 204268). This premature translational stop signal has been observed in individual(s) with primary hyperoxaluria (PMID: 22391140). This variant is present in population databases (rs746419489, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Tyr39*) in the HOGA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HOGA1 are known to be pathogenic (PMID: 22391140, 22781098). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at