16-20348994-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003361.4(UMOD):​c.307G>A​(p.Gly103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,577,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

UMOD
NM_003361.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28355813).
BS2
High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UMODNM_003361.4 linkuse as main transcriptc.307G>A p.Gly103Ser missense_variant 3/11 ENST00000396138.9 NP_003352.2 P07911-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UMODENST00000396138.9 linkuse as main transcriptc.307G>A p.Gly103Ser missense_variant 3/115 NM_003361.4 ENSP00000379442.5 P07911-1X6RBG4
UMODENST00000396134.6 linkuse as main transcriptc.406G>A p.Gly136Ser missense_variant 4/122 ENSP00000379438.2 P07911-5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000528
AC:
1
AN:
189332
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
101786
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000200
GnomAD4 exome
AF:
0.0000168
AC:
24
AN:
1425188
Hom.:
0
Cov.:
39
AF XY:
0.0000184
AC XY:
13
AN XY:
705662
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000267
Gnomad4 SAS exome
AF:
0.0000489
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000165
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial juvenile hyperuricemic nephropathy type 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJan 06, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;.;.;.;T;.;.;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.81
T;D;D;.;D;D;T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.28
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
1.2
.;.;L;L;.;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.53
N;.;N;.;.;.;.;.
REVEL
Uncertain
0.32
Sift
Benign
0.11
T;.;T;.;.;.;.;.
Sift4G
Uncertain
0.014
D;D;D;D;.;.;D;D
Polyphen
0.57
.;.;P;P;.;.;.;.
Vest4
0.22
MVP
0.54
MPC
1.5
ClinPred
0.93
D
GERP RS
4.5
Varity_R
0.035
gMVP
0.83

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28934584; hg19: chr16-20360316; API