chr16-20348509-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001378234.1(UMOD):c.792G>A(p.Val264Val) 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_001378234.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0900

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant medullary cystic kidney disease with or without hyperuricemia
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
glomerulocystic kidney disease with hyperuricemia and isosthenuria
Inheritance: AD Classification: DEFINITIVE Submitted by: Laboratory for Molecular Medicine
familial juvenile hyperuricemic nephropathy type 1
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant medullary cystic kidney disease with hyperuricemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

UMOD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious 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 VariationId is 94131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378234.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UMOD	NM_003361.4	MANE Select	c.792G>A	p.Val264Val	synonymous	Exon 3 of 11	NP_003352.2
UMOD	NM_001378234.1		c.792G>A	p.Val264Val	synonymous	Exon 3 of 12	NP_001365163.1
UMOD	NM_001378235.1		c.792G>A	p.Val264Val	synonymous	Exon 3 of 12	NP_001365164.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UMOD	ENST00000396138.9	TSL:5 MANE Select	c.792G>A	p.Val264Val	synonymous	Exon 3 of 11	ENSP00000379442.5
UMOD	ENST00000396134.6	TSL:2	c.891G>A	p.Val297Val	synonymous	Exon 4 of 12	ENSP00000379438.2
UMOD	ENST00000863077.1		c.954G>A	p.Val318Val	synonymous	Exon 4 of 12	ENSP00000533136.1

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

GnomAD2 exomes

AF:

0.156

AC:

37266

AN:

239420

AF XY:

0.158

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 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

African (AFR)

AF:

0.112

AC:

3751

AN:

33478

American (AMR)

AF:

0.152

AC:

6728

AN:

44388

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3543

AN:

26086

East Asian (EAS)

AF:

0.00489

AC:

194

AN:

39658

South Asian (SAS)

AF:

0.159

AC:

13647

AN:

85986

European-Finnish (FIN)

AF:

0.223

AC:

11036

AN:

49510

Middle Eastern (MID)

AF:

0.197

AC:

1134

AN:

5764

European-Non Finnish (NFE)

AF:

0.180

AC:

200316

AN:

1111102

Other (OTH)

AF:

0.165

AC:

9928

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

14895

29790

44686

59581

74476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6970

13940

20910

27880

34850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23568

AN:

152304

Hom.:

2000

Cov.:

AF XY:

0.156

AC XY:

11614

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.104

AC:

4314

AN:

41582

American (AMR)

AF:

0.176

AC:

2700

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3470

East Asian (EAS)

AF:

0.0112

AC:

AN:

5180

South Asian (SAS)

AF:

0.147

AC:

709

AN:

4828

European-Finnish (FIN)

AF:

0.225

AC:

2390

AN:

10606

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12253

AN:

68006

Other (OTH)

AF:

0.165

AC:

349

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1055

2110

3165

4220

5275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

5599

Bravo

AF:

0.149

Asia WGS

AF:

0.107

AC:

371

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Familial juvenile hyperuricemic nephropathy type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.090

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over