16-20348509-C-T

Position:

chr16-20348509-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_003361.4(UMOD):c.792G>A(p.Val264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,608,538 control chromosomes in the GnomAD database, including 24,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2000 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22479 hom. )

Consequence

UMOD
NM_003361.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0900

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]

UMOD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 16-20348509-C-T is Benign according to our data. Variant chr16-20348509-C-T is described in ClinVar as [Benign]. Clinvar id is 94131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-20348509-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMOD	NM_003361.4 linkuse as main transcript	c.792G>A	p.Val264=	synonymous_variant	3/11	ENST00000396138.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMOD	ENST00000396138.9 linkuse as main transcript	c.792G>A	p.Val264=	synonymous_variant	3/11	5	NM_003361.4	P2	P07911-1
UMOD	ENST00000396134.6 linkuse as main transcript	c.891G>A	p.Val297=	synonymous_variant	4/12	2		A2	P07911-5
UMOD	ENST00000570689.5 linkuse as main transcript	c.792G>A	p.Val264=	synonymous_variant	3/11	5		P2	P07911-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23544

AN:

152186

Hom.:

1994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.156

AC:

37266

AN:

239420

Hom.:

3208

AF XY:

0.158

AC XY:

20704

AN XY:

130638

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.172

AC:

250277

AN:

1456234

Hom.:

22479

Cov.:

AF XY:

0.171

AC XY:

124248

AN XY:

724482

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.00489

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.155

AC:

23568

AN:

152304

Hom.:

2000

Cov.:

AF XY:

0.156

AC XY:

11614

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.164

Hom.:

2413

Bravo

AF:

0.149

Asia WGS

AF:

0.107

AC:

371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 10, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 22, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Familial juvenile hyperuricemic nephropathy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.51

Position offset: 3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over