16-20348311-C-T

Variant names:

• chr16-20348311-C-T
• rs28544423
• NM_003361.4:c.885G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003361.4(UMOD):​c.885G>A​(p.Gly295Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,614,024 control chromosomes in the GnomAD database, including 25,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1916 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23243 hom.)
• Consequence: UMOD NM_003361.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.49

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-20348311-C-T is Benign according to our data. Variant chr16-20348311-C-T is described in ClinVar as [Benign]. Clinvar id is 94132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-20348311-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
UMOD	NM_003361.4	c.885G>A	p.Gly295Gly	synonymous_variant	Exon 4 of 11	ENST00000396138.9	NP_003352.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000396138.9	c.885G>A	p.Gly295Gly	synonymous_variant	Exon 4 of 11	5	NM_003361.4	ENSP00000379442.5
UMOD	ENST00000396134.6	c.984G>A	p.Gly328Gly	synonymous_variant	Exon 5 of 12	2		ENSP00000379438.2
UMOD	ENST00000570689.5	c.885G>A	p.Gly295Gly	synonymous_variant	Exon 4 of 11	5		ENSP00000460548.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22644 AN: 152168 Hom.: 1912 Cov.: 33

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.159 AC: 40022 AN: 251440 Hom.: 3658 AF XY: 0.164 AC XY: 22241 AN XY: 135896

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.0117

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.174 AC: 254267 AN: 1461738 Hom.: 23243 Cov.: 36 AF XY: 0.175 AC XY: 126913 AN XY: 727182

Gnomad4 AFR exome AF: 0.0835

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.00562

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.149 AC: 22648 AN: 152286 Hom.: 1916 Cov.: 33 AF XY: 0.151 AC XY: 11206 AN XY: 74456

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.158

Alfa AF: 0.147 Hom.: 1014

Bravo AF: 0.141

Asia WGS AF: 0.0990 AC: 348 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.186

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 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

Mar 10, 2015

Eurofins Ntd Llc (ga)

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	4.6
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs28544423; hg19: chr16-20359633; COSMIC: COSV56773565; COSMIC: COSV56773565;