NM_000458.4(HNF1B):c.107C>T (p.Ser36Phe) AND Maturity onset diabetes mellitus in young

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001248883.5

Allele description [Variation Report for NM_000458.4(HNF1B):c.107C>T (p.Ser36Phe)]

NM_000458.4(HNF1B):c.107C>T (p.Ser36Phe)

Gene:

HNF1B:HNF1 homeobox B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_000458.4(HNF1B):c.107C>T (p.Ser36Phe)

Other names:

NM_000458.4:c.107C>T

HGVS:

NC_000017.11:g.37744778G>A
NG_013019.2:g.5329C>T
NM_000458.4:c.107C>TMANE SELECT
NM_001165923.4:c.107C>T
NM_001304286.2:c.107C>T
NP_000449.1:p.Ser36Phe
NP_001159395.1:p.Ser36Phe
NP_001291215.1:p.Ser36Phe
NC_000017.10:g.36104769G>A
NC_000017.10:g.36104769G>A
NM_000458.3:c.107C>T

Protein change:

S36F

Links:

Molecular consequence:

NM_000458.4:c.107C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165923.4:c.107C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304286.2:c.107C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity onset diabetes mellitus in young (MODY)
Synonyms:: Mason type diabetes
Identifiers:: MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001422563	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 11845238, 25741868 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001422563

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

germline

curation

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Identification of a gain-of-function mutation in the HNF-1beta gene in a Japanese family with MODY.

Yoshiuchi I, Yamagata K, Zhu Q, Tamada I, Takahashi Y, Onigata K, Takeda J, Miyagawa J, Matsuzawa Y.

Diabetologia. 2002 Jan;45(1):154-5. No abstract available.

PubMed [citation]

PMID:: 11845238

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

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001422563.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

The p.Ser36Phe variant in HNF1B has been reported in 3 Japanese individuals with MODY (PMID: 11845238), and has been identified in 0.2% (36/19922) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs544890850). This variant has been seen in the general population at a frequency high enough to rule out a pathogenic role. In vitro functional studies provide some evidence that the p.Ser36Phe variant may slightly impact protein function (PMID: 11845238). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser36Phe variant is uncertain. ACMG/AMP Criteria applied: BA1, PS3_supporting (Richards 2015).

#	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: Nov 3, 2024

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