rs77875418
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003361.4(UMOD):c.264C>T(p.Gly88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,598,442 control chromosomes in the GnomAD database, including 839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.028 ( 151 hom., cov: 33)
Exomes 𝑓: 0.011 ( 688 hom. )
Consequence
UMOD
NM_003361.4 synonymous
NM_003361.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.63
Genes affected
UMOD (HGNC:12559): (uromodulin) The protein encoded by this gene is the most abundant protein in mammalian urine under physiological conditions. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. This protein may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of this protein in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the renal disorders medullary cystic kidney disease-2 (MCKD2), glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI), and familial juvenile hyperuricemic nephropathy (FJHN). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 16-20349037-G-A is Benign according to our data. Variant chr16-20349037-G-A is described in ClinVar as [Benign]. Clinvar id is 259046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-20349037-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.63 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UMOD | NM_003361.4 | c.264C>T | p.Gly88= | synonymous_variant | 3/11 | ENST00000396138.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UMOD | ENST00000396138.9 | c.264C>T | p.Gly88= | synonymous_variant | 3/11 | 5 | NM_003361.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0281 AC: 4273AN: 152264Hom.: 151 Cov.: 33
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GnomAD3 exomes AF: 0.0311 AC: 6901AN: 222184Hom.: 287 AF XY: 0.0316 AC XY: 3801AN XY: 120328
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GnomAD4 exome AF: 0.0113 AC: 16376AN: 1446060Hom.: 688 Cov.: 39 AF XY: 0.0134 AC XY: 9649AN XY: 718098
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GnomAD4 genome ? AF: 0.0281 AC: 4285AN: 152382Hom.: 151 Cov.: 33 AF XY: 0.0305 AC XY: 2273AN XY: 74522
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial juvenile hyperuricemic nephropathy type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at