NM_000458.4(HNF1B):c.140C>T (p.Pro47Leu) AND Renal cysts and diabetes syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 22, 2020
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:: RCV000787252.9

Allele description [Variation Report for NM_000458.4(HNF1B):c.140C>T (p.Pro47Leu)]

NM_000458.4(HNF1B):c.140C>T (p.Pro47Leu)

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.140C>T (p.Pro47Leu)

HGVS:

NC_000017.11:g.37744745G>A
NG_013019.2:g.5362C>T
NM_000458.3(HNF1B):c.140C>T
NM_000458.4:c.140C>TMANE SELECT
NM_001165923.4:c.140C>T
NM_001304286.2:c.140C>T
NP_000449.1:p.Pro47Leu
NP_001159395.1:p.Pro47Leu
NP_001291215.1:p.Pro47Leu
NC_000017.10:g.36104736G>A
NC_000017.10:g.36104736G>A
NM_000458.2:c.140C>T
NM_000458.3(HNF1B):c.140C>T
NM_000458.3:c.140C>T
NM_000458.4:c.140C>T

Protein change:

P47L

Links:

Molecular consequence:

NM_000458.4:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165923.4:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304286.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Renal cysts and diabetes syndrome (RCAD)
Synonyms:: Maturity-onset diabetes of the young, type 5; MODY type 5; Hyperuricemic nephropathy, familial juvenile, atypical; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007669; MedGen: C0431693; Orphanet: 93111; OMIM: 137920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000926182	Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 6, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001423106	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 (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000926182

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 6, 2019)

germline

literature only

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

SCV001423106

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

Citation Link

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	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

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

Details of each submission

From Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, SCV000926182.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001423106.2

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

Description

The p.Pro47Leu variant in HNF1B has been reported in at least 1 individual with Renal Cysts and Diabetes Syndrome in ClinVar (Variation ID: 36840), and has been identified in 0.02024% (7/34580) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs193922483). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a carrier frequency. Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant has also been reported likely pathogenic in ClinVar (Variation ID: 36840). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro47Leu variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3 (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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