chr16-20349037-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003361.4(UMOD):c.264C>T(p.Gly88Gly) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.63

Publications

7 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 -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 VariationId is 259046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
UMOD	NM_003361.4 link	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 11	ENST00000396138.9	NP_003352.2	P07911-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000396138.9 link	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 11	5	NM_003361.4	ENSP00000379442.5		P07911-1X6RBG4
UMOD	ENST00000396134.6 link	c.363C>T	p.Gly121Gly	synonymous_variant	Exon 4 of 12	2		ENSP00000379438.2		P07911-5

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4273

AN:

152264

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0614

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0311

AC:

6901

AN:

222184

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.0646

Gnomad AMR exome

AF:

0.0699

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.00165

Gnomad NFE exome

AF:

0.000711

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0113

AC:

16376

AN:

1446060

Hom.:

688

Cov.:

AF XY:

0.0134

AC XY:

9649

AN XY:

718098

show subpopulations

African (AFR)

AF:

0.0651

AC:

2150

AN:

33040

American (AMR)

AF:

0.0678

AC:

2859

AN:

42146

Ashkenazi Jewish (ASJ)

AF:

0.0000774

AC:

AN:

25828

East Asian (EAS)

AF:

0.0542

AC:

2098

AN:

38716

South Asian (SAS)

AF:

0.0934

AC:

7836

AN:

83884

European-Finnish (FIN)

AF:

0.00190

AC:

AN:

52104

Middle Eastern (MID)

AF:

0.00626

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000309

AC:

341

AN:

1104694

Other (OTH)

AF:

0.0159

AC:

955

AN:

59896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1273

2546

3819

5092

6365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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:

0.0281

AC:

4285

AN:

152382

Hom.:

151

Cov.:

AF XY:

0.0305

AC XY:

2273

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.0636

AC:

2644

AN:

41590

American (AMR)

AF:

0.0485

AC:

742

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0617

AC:

320

AN:

5184

South Asian (SAS)

AF:

0.105

AC:

506

AN:

4832

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68044

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

202

404

607

809

1011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0142

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 14, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial juvenile hyperuricemic nephropathy type 1

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.1

(source)

DANN

Benign

0.55

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over