rs7193058

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003361.4(UMOD):​c.522C>T​(p.Cys174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,543,230 control chromosomes in the GnomAD database, including 396,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35967 hom., cov: 35)
Exomes 𝑓: 0.71 ( 360908 hom. )

Consequence

UMOD
NM_003361.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.93
Variant links:
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=-0.6).
BP6
Variant 16-20348779-G-A is Benign according to our data. Variant chr16-20348779-G-A is described in ClinVar as [Benign]. Clinvar id is 94130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-20348779-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.93 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UMODNM_003361.4 linkuse as main transcriptc.522C>T p.Cys174= synonymous_variant 3/11 ENST00000396138.9 NP_003352.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UMODENST00000396138.9 linkuse as main transcriptc.522C>T p.Cys174= synonymous_variant 3/115 NM_003361.4 ENSP00000379442 P2P07911-1
UMODENST00000396134.6 linkuse as main transcriptc.621C>T p.Cys207= synonymous_variant 4/122 ENSP00000379438 A2P07911-5
UMODENST00000570689.5 linkuse as main transcriptc.522C>T p.Cys174= synonymous_variant 3/115 ENSP00000460548 P2P07911-1

Frequencies

GnomAD3 genomes
AF:
0.680
AC:
103430
AN:
152068
Hom.:
35948
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.678
Gnomad AMI
AF:
0.681
Gnomad AMR
AF:
0.573
Gnomad ASJ
AF:
0.725
Gnomad EAS
AF:
0.308
Gnomad SAS
AF:
0.459
Gnomad FIN
AF:
0.663
Gnomad MID
AF:
0.690
Gnomad NFE
AF:
0.749
Gnomad OTH
AF:
0.696
GnomAD3 exomes
AF:
0.615
AC:
88092
AN:
143242
Hom.:
28928
AF XY:
0.616
AC XY:
47561
AN XY:
77240
show subpopulations
Gnomad AFR exome
AF:
0.669
Gnomad AMR exome
AF:
0.488
Gnomad ASJ exome
AF:
0.722
Gnomad EAS exome
AF:
0.306
Gnomad SAS exome
AF:
0.483
Gnomad FIN exome
AF:
0.677
Gnomad NFE exome
AF:
0.747
Gnomad OTH exome
AF:
0.651
GnomAD4 exome
AF:
0.713
AC:
991150
AN:
1391042
Hom.:
360908
Cov.:
100
AF XY:
0.707
AC XY:
484861
AN XY:
686050
show subpopulations
Gnomad4 AFR exome
AF:
0.668
Gnomad4 AMR exome
AF:
0.497
Gnomad4 ASJ exome
AF:
0.727
Gnomad4 EAS exome
AF:
0.303
Gnomad4 SAS exome
AF:
0.483
Gnomad4 FIN exome
AF:
0.678
Gnomad4 NFE exome
AF:
0.754
Gnomad4 OTH exome
AF:
0.687
GnomAD4 genome
AF:
0.680
AC:
103484
AN:
152188
Hom.:
35967
Cov.:
35
AF XY:
0.666
AC XY:
49581
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.678
Gnomad4 AMR
AF:
0.572
Gnomad4 ASJ
AF:
0.725
Gnomad4 EAS
AF:
0.308
Gnomad4 SAS
AF:
0.461
Gnomad4 FIN
AF:
0.663
Gnomad4 NFE
AF:
0.749
Gnomad4 OTH
AF:
0.693
Alfa
AF:
0.731
Hom.:
14370
Bravo
AF:
0.671
Asia WGS
AF:
0.414
AC:
1441
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:6
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsOct 07, 2020- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 19, 2016- -
not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 25, 2019- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Familial juvenile hyperuricemic nephropathy type 1 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
9.1
DANN
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7193058; hg19: chr16-20360101; COSMIC: COSV56773657; COSMIC: COSV56773657; API