NM_003361.4(UMOD):c.816C>A (p.Tyr272Ter) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 31, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000578929.4

Allele description [Variation Report for NM_003361.4(UMOD):c.816C>A (p.Tyr272Ter)]

NM_003361.4(UMOD):c.816C>A (p.Tyr272Ter)

Gene:

UMOD:uromodulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.3

Genomic location:

Preferred name:

NM_003361.4(UMOD):c.816C>A (p.Tyr272Ter)

HGVS:

NC_000016.10:g.20348485G>T
NG_008151.1:g.9231C>A
NM_001008389.3:c.816C>A
NM_001278614.2:c.915C>A
NM_001378232.1:c.816C>A
NM_001378233.1:c.816C>A
NM_001378234.1:c.816C>A
NM_001378235.1:c.816C>A
NM_001378237.1:c.816C>A
NM_003361.4:c.816C>AMANE SELECT
NP_001008390.1:p.Tyr272Ter
NP_001265543.1:p.Tyr305Ter
NP_001365161.1:p.Tyr272Ter
NP_001365162.1:p.Tyr272Ter
NP_001365163.1:p.Tyr272Ter
NP_001365164.1:p.Tyr272Ter
NP_001365166.1:p.Tyr272Ter
NP_003352.2:p.Tyr272Ter
NC_000016.9:g.20359807G>T
NM_003361.2:c.816C>A
NR_165456.1:n.1041C>A

Protein change:

Y272*

Links:

dbSNP: rs141383844

NCBI 1000 Genomes Browser:

rs141383844

Molecular consequence:

NR_165456.1:n.1041C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001008389.3:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001278614.2:c.915C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001378232.1:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001378233.1:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001378234.1:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001378235.1:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001378237.1:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003361.4:c.816C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Profile neighbors for GEO Profiles (Select 88639253) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 88636828) (20)
GEO Profiles
cytochrome b, partial (mitochondrion) [Plasmodium sp. BULIBP75]
cytochrome b, partial (mitochondrion) [Plasmodium sp. BULIBP75]
gi|1569122895|gb|QBA89589.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000681209	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Dec 8, 2017)	germline	clinical testing	Citation Link,
SCV002936928	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000681209

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Dec 8, 2017)

germline

clinical testing

Citation Link,

SCV002936928

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000681209.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The Y272X variant in the UMOD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay, however, loss-of-function is not a known mechanism of disease for the UMOD gene. The Y272X variant is observed in 3/270,990 total alleles in large population cohorts (Lek et al., 2016). We interpret Y272X as a variant of uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002936928.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. ClinVar contains an entry for this variant (Variation ID: 489216). This variant has not been reported in the literature in individuals affected with UMOD-related conditions. This variant is present in population databases (rs141383844, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Tyr272*) in the UMOD gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in UMOD cause disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine