NM_000545.8(HNF1A):c.1107+9C>G AND Maturity-onset diabetes of the young type 3

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Jan 13, 2018
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:: RCV000030475.7

Allele description [Variation Report for NM_000545.8(HNF1A):c.1107+9C>G]

NM_000545.8(HNF1A):c.1107+9C>G

Gene:

HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000545.8(HNF1A):c.1107+9C>G

HGVS:

NC_000012.12:g.120996422C>G
NG_011731.2:g.22677C>G
NM_000545.8:c.1107+9C>GMANE SELECT
NM_001306179.2:c.1107+9C>G
LRG_522t1:c.1107+9C>G
LRG_522:g.22677C>G
NC_000012.11:g.121434225C>G
NM_000545.5:c.1107+9C>G
NM_000545.6:c.1107+9C>G

Links:

dbSNP: rs17847497

NCBI 1000 Genomes Browser:

rs17847497

Molecular consequence:

NM_000545.8:c.1107+9C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001306179.2:c.1107+9C>G - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Maturity-onset diabetes of the young type 3
Synonyms:: Diabetes mellitus MODY type 3; MODY hepatocyte nuclear factor-1-alpha related; MODY type 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010894; MedGen: C1838100; Orphanet: 552; OMIM: 600496

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053145	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	likely benign (Aug 18, 2011)	germline	curation, clinical testing	PubMed (6) [See all records that cite these PMIDs] 10634407, 17407072, 18811724, 9287053, 16834925, 10588527 Citation Link,
SCV000376716	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000053145

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

likely benign
(Aug 18, 2011)

germline

curation, clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV000376716

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	3	not provided	curation
not provided	germline	unknown	8	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification and functional analysis of mutations in the hepatocyte nuclear factor-1alpha gene in anti-islet autoantibody-negative Japanese patients with type 1 diabetes.

Kawasaki E, Sera Y, Yamakawa K, Abe T, Ozaki M, Uotani S, Ohtsu N, Takino H, Yamasaki H, Yamaguchi Y, Matsuura N, Eguchi K.

J Clin Endocrinol Metab. 2000 Jan;85(1):331-5.

PubMed [citation]

PMID:: 10634407

[The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes].

Yang Z, Wu SH, Zheng TS, Wang SJ, Lu HJ, Xiang KS.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Apr;24(2):157-61. Chinese.

PubMed [citation]

PMID:: 17407072

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000053145.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	curation	PubMed (6)
2	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
3	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
4	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
5	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
6	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
7	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
8	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)
9	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

"Found at allele frequency of .02 in cohort of 92 MODY patients (this calculates to be 3.68 alleles; zygosity not specified; counted 3 here); not found in 200 normal chromosomes (see pbGP)": PubMed [ID: 10588527]

Description

Converted during submission to Likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	3	not provided	not provided		3	not provided	not provided	not provided
2	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 2
3	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 3
4	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 4
5	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 5
6	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 6
7	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 7
8	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 8
9	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 9

Co-occurrences

#	Zygosity	Alleles	Number of Observations
2	SingleHeterozygote	GCK:c.1253+8C>T, HNF4A:c.116-5C>T, IPF1:c.292G>A, TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.1501+7G>A, TCF1:c.1720A>G	1
3	Homozygote	TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1720A>G, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.1501+7G>A	1
4	SingleHeterozygote	GCK:c.1253+8C>T, HNF4A:c.116-5C>T, TCF1:c.79A>C, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.51C>G, TCF1:c.1720A>G	1
5	SingleHeterozygote	HNF4A:c.116-5C>T, TCF1:c.51C>G, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.79A>C, TCF1:c.1720A>G, TCF2:c.703C>T	1
6	SingleHeterozygote	GCK:c.1253+8C>T, TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1720A>G, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T	1
7	SingleHeterozygote	GCK:c.1253+8C>T, GCK:c.542T>C, TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.1720A>G	1
8	Homozygote	TCF2:c.703C>T	1
9	SingleHeterozygote	HNF4A:c.116-5C>T, TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.1720A>G, TCF2:c.511T>C	1

From Illumina Laboratory Services, Illumina, SCV000376716.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this 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: May 26, 2024

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