rs796052090
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM5PP3_StrongPP5
The NM_138413.4(HOGA1):c.533T>A(p.Leu178Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,072 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. L178P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_138413.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOGA1 | NM_138413.4 | c.533T>A | p.Leu178Gln | missense_variant | 4/7 | ENST00000370646.9 | |
HOGA1 | NM_001134670.2 | c.212-2113T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOGA1 | ENST00000370646.9 | c.533T>A | p.Leu178Gln | missense_variant | 4/7 | 1 | NM_138413.4 | P1 | |
HOGA1 | ENST00000370647.8 | c.212-2113T>A | intron_variant | 1 | |||||
HOGA1 | ENST00000465608.1 | n.1377T>A | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Primary hyperoxaluria type 3 Pathogenic:1Uncertain: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:PM2, PM3 PP3 PP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 28, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces leucine with glutamine at codon 178 of the HOGA1 protein (p.Leu178Gln). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). 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