rs77875418

Positions:

chr16-20349037-G-A

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.63

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 -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 linkuse as main transcript	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 linkuse as main transcript	c.264C>T	p.Gly88=	synonymous_variant	3/11	5	NM_003361.4	P2	P07911-1

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

GnomAD3 exomes

AF:

0.0311

AC:

6901

AN:

222184

Hom.:

287

AF XY:

0.0316

AC XY:

3801

AN XY:

120328

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 SAS exome

AF:

0.0965

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

Gnomad4 AFR exome

AF:

0.0651

Gnomad4 AMR exome

AF:

0.0678

Gnomad4 ASJ exome

AF:

0.0000774

Gnomad4 EAS exome

AF:

0.0542

Gnomad4 SAS exome

AF:

0.0934

Gnomad4 FIN exome

AF:

0.00190

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0281

AC:

4285

AN:

152382

Hom.:

151

Cov.:

AF XY:

0.0305

AC XY:

2273

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.0485

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0617

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.1

DANN

Benign

0.55

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

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