rs1555487316
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_003361.4(UMOD):c.949T>G(p.Cys317Gly) 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. C317Y) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003361.4 missense
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 |
---|---|---|---|---|---|---|---|
UMOD | NM_003361.4 | c.949T>G | p.Cys317Gly | missense_variant | 4/11 | ENST00000396138.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UMOD | ENST00000396138.9 | c.949T>G | p.Cys317Gly | missense_variant | 4/11 | 5 | NM_003361.4 | P2 | |
UMOD | ENST00000396134.6 | c.1048T>G | p.Cys350Gly | missense_variant | 5/12 | 2 | A2 | ||
UMOD | ENST00000570689.5 | c.949T>G | p.Cys317Gly | missense_variant | 4/11 | 5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial juvenile hyperuricemic nephropathy type 1 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences | Feb 03, 2015 | The affected residue locates within the cysteine‑rich 2 domain and is immediately preceded by a highly conserved cysteine residue. Various bioinformatics tools such as mutation taster, PolyPhen and Sorting Intolerant from Tolerant also predicted it to be pathogenic. This amino acid residue is conserved across other animal species. Based on the above evidence, we concluded that this novel variant is very likely the causal pathogenic mutation. - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at