chr10-97601889-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM5PP3_ModeratePP5
The NM_138413.4(HOGA1):c.733G>T(p.Val245Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,612,556 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V245I) has been classified as Pathogenic.
Frequency
Consequence
NM_138413.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOGA1 | NM_138413.4 | c.733G>T | p.Val245Phe | missense_variant | 6/7 | ENST00000370646.9 | |
HOGA1 | NM_001134670.2 | c.244G>T | p.Val82Phe | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOGA1 | ENST00000370646.9 | c.733G>T | p.Val245Phe | missense_variant | 6/7 | 1 | NM_138413.4 | P1 | |
HOGA1 | ENST00000370647.8 | c.244G>T | p.Val82Phe | missense_variant | 2/3 | 1 | |||
HOGA1 | ENST00000370642.4 | c.145G>T | p.Val49Phe | missense_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152270Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250612Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135532
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1460286Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726438
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74390
ClinVar
Submissions by phenotype
Primary hyperoxaluria type 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Rare Kidney Stone Consortium and the Mayo Clinic Hyperoxaluria Center, Mayo Clinic | Oct 27, 2023 | ACMG:PM1 PM2 PM3 PM5 PP3 - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2021 | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 245 of the HOGA1 protein (p.Val245Phe). This variant is present in population databases (rs755562733, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with HOGA1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HOGA1 protein function. 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