rs28934584
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_003361.4(UMOD):c.307G>T(p.Gly103Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G103D) has been classified as Uncertain significance.
Frequency
Consequence
NM_003361.4 missense
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 | UniProt |
---|---|---|---|---|---|---|---|
UMOD | NM_003361.4 | c.307G>T | p.Gly103Cys | missense_variant | 3/11 | ENST00000396138.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UMOD | ENST00000396138.9 | c.307G>T | p.Gly103Cys | missense_variant | 3/11 | 5 | NM_003361.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 39
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial juvenile hyperuricemic nephropathy type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2002 | - - |
UMOD-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 29, 2023 | The UMOD c.307G>T variant is predicted to result in the amino acid substitution p.Gly103Cys. This variant was reported to segregate with medullary cystic kidney disease 2 in three affected and five unaffected individuals from a single family (Family 3, Hart et al 2002. PubMed ID: 12471200), and has also been reported in one unrelated individual with autosomal dominant tubulointerstitial kidney disease (Table S1, Olinger et al. 2020. PubMed ID: 32450155). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at