rs13329952

Variant names:

• chr16-20355185-T-C
• rs13329952
• ENST00000570689.5:c.-40+1009A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570689.5(UMOD):​c.-40+1009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,926 control chromosomes in the GnomAD database, including 4,680 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4680 hom., cov: 31)
• Consequence: UMOD ENST00000570689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 23 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMOD	XM_011545938.1	c.-40+1009A>G		intron_variant	Intron 1 of 11		XP_011544240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000570689.5	c.-40+1009A>G		intron_variant	Intron 1 of 10	5		ENSP00000460548.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36377 AN: 151808 Hom.: 4673 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.240 AC: 36405 AN: 151926 Hom.: 4680 Cov.: 31 AF XY: 0.242 AC XY: 17998 AN XY: 74220

African (AFR) AF: 0.329 AC: 13630 AN: 41406

American (AMR) AF: 0.252 AC: 3841 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3464

East Asian (EAS) AF: 0.0733 AC: 378 AN: 5156

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4810

European-Finnish (FIN) AF: 0.233 AC: 2458 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13161 AN: 67966

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.205 Hom.: 4486

Bravo AF: 0.242

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.87
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13329952; hg19: chr16-20366507;