rs180177304
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_012203.2(GRHPR):c.102G>A(p.Trp34Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,270 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_012203.2 stop_gained
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 | UniProt |
---|---|---|---|---|---|---|---|
GRHPR | NM_012203.2 | c.102G>A | p.Trp34Ter | stop_gained | 2/9 | ENST00000318158.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHPR | ENST00000318158.11 | c.102G>A | p.Trp34Ter | stop_gained | 2/9 | 1 | NM_012203.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461072Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726866
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type II Pathogenic:3
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 31, 2020 | - - |
Pathogenic, no assertion criteria provided | research | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 29, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2023 | This sequence change creates a premature translational stop signal (p.Trp34*) in the GRHPR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRHPR are known to be pathogenic (PMID: 25644115). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with primary hyperoxaluria type 2 (PMID: 25629080, 31685312). ClinVar contains an entry for this variant (Variation ID: 204231). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at