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NM_003361.4(UMOD):c.326T>A (p.Val109Glu) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Sep 12, 2022
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000681768.7

Allele description [Variation Report for NM_003361.4(UMOD):c.326T>A (p.Val109Glu)]

NM_003361.4(UMOD):c.326T>A (p.Val109Glu)

Gene:
UMOD:uromodulin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p12.3
Genomic location:
Preferred name:
NM_003361.4(UMOD):c.326T>A (p.Val109Glu)
HGVS:
  • NC_000016.10:g.20348975A>T
  • NG_008151.1:g.8741T>A
  • NM_001008389.2:c.326T>A
  • NM_001008389.3:c.326T>A
  • NM_001278614.2:c.425T>A
  • NM_001378232.1:c.326T>A
  • NM_001378233.1:c.326T>A
  • NM_001378234.1:c.326T>A
  • NM_001378235.1:c.326T>A
  • NM_001378237.1:c.326T>A
  • NM_003361.4:c.326T>AMANE SELECT
  • NP_001008390.1:p.Val109Glu
  • NP_001265543.1:p.Val142Glu
  • NP_001365161.1:p.Val109Glu
  • NP_001365162.1:p.Val109Glu
  • NP_001365163.1:p.Val109Glu
  • NP_001365164.1:p.Val109Glu
  • NP_001365166.1:p.Val109Glu
  • NP_003352.2:p.Val109Glu
  • NC_000016.9:g.20360297A>T
  • NM_003361.3:c.326T>A
  • NR_165456.1:n.551T>A
Protein change:
V109E
Links:
dbSNP: rs780462125
NCBI 1000 Genomes Browser:
rs780462125
Molecular consequence:
  • NM_001008389.3:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278614.2:c.425T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378232.1:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378233.1:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378234.1:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378235.1:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378237.1:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003361.4:c.326T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_165456.1:n.551T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000809229Gharavi Laboratory, Columbia University
no assertion criteria provided

(ACMG Guidelines, 2015)
Likely pathogenic
(Sep 16, 2018)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

SCV001446847Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Oct 23, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002231057Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Sep 12, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot provided1not providedclinical testing, research
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Novel UMOD mutations in familial juvenile hyperuricemic nephropathy lead to abnormal uromodulin intracellular trafficking.

Liu M, Chen Y, Liang Y, Liu Y, Wang S, Hou P, Zhang H, Zhao M.

Gene. 2013 Dec 1;531(2):363-9. doi: 10.1016/j.gene.2013.08.041. Epub 2013 Aug 27.

PubMed [citation]
PMID:
23988501
See all PubMed Citations (3)

Details of each submission

From Gharavi Laboratory, Columbia University, SCV000809229.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446847.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

From Invitae, SCV002231057.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on UMOD protein function. ClinVar contains an entry for this variant (Variation ID: 562322). This missense change has been observed in individual(s) with autosomal dominant medullary cystic kidney disease (PMID: 23988501). This variant is present in population databases (rs780462125, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 109 of the UMOD protein (p.Val109Glu). Experimental studies have shown that this missense change affects UMOD function (PMID: 23988501). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024