rs771019056
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_012203.2(GRHPR):c.454dup(p.Thr152AsnfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L151L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_012203.2 frameshift
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.454dup | p.Thr152AsnfsTer39 | frameshift_variant | 5/9 | ENST00000318158.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHPR | ENST00000318158.11 | c.454dup | p.Thr152AsnfsTer39 | frameshift_variant | 5/9 | 1 | NM_012203.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250342Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135380
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459874Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726348
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type II Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 06, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 06, 2016 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 18, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change creates a premature translational stop signal (p.Thr152Asnfs*39) 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 present in population databases (rs771019056, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with primary hyperoxaluria (PMID: 25644115, 28569194). ClinVar contains an entry for this variant (Variation ID: 371016). 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