Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000545.8(HNF1A):c.-6C>T

CA6831648

307454 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: df141907-2286-41e0-855a-0951fe1419e3
Approved on: 2025-11-26
Published on: 2025-11-26

HGVS expressions

NM_000545.8:c.-6C>T
NM_000545.8(HNF1A):c.-6C>T
NC_000012.12:g.120978763C>T
CM000674.2:g.120978763C>T
NC_000012.11:g.121416566C>T
CM000674.1:g.121416566C>T
NC_000012.10:g.119900949C>T
NG_011731.2:g.5018C>T
ENST00000560968.6:c.-6C>T
ENST00000257555.11:c.-6C>T
ENST00000257555.10:c.-6C>T
ENST00000400024.6:c.-6C>T
ENST00000402929.5:n.130C>T
ENST00000535955.5:n.42+71C>T
ENST00000538626.2:n.113C>T
ENST00000538646.5:c.-6C>T
ENST00000540108.1:c.-6C>T
ENST00000541395.5:c.-6C>T
ENST00000541924.5:c.-6C>T
ENST00000543427.5:c.-6C>T
ENST00000544413.2:c.-6C>T
ENST00000544574.5:c.-6C>T
ENST00000560968.5:c.138C>T
ENST00000615446.4:c.-258+52C>T
ENST00000617366.4:c.-6C>T
NM_000545.5:c.-6C>T
NM_000545.6:c.-6C>T
NM_001306179.1:c.-6C>T
NM_001306179.2:c.-6C>T
More

Uncertain Significance

Not Met criteria codes 4
BS1 PS4 PP4 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 3.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.-6C>T variant in the HNF1 homeobox A gene, HNF1A, is a single nucleotide variant within the 5'UTR of NM_000545.8. This variant has a Grpmax filtering allele frequency of 0.00001773 in gnomAD v4.1.0, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (internal lab contributors), thus PP4 cannot be applied. In summary, c.-6C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 3.1.0 approved 10/10/2025): none.
Not Met criteria codes
BS1
This variant has a Grpmax filtering allele frequency of 0.00001773 in gnomAD v4.1.0, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% [internal lab contributors].
PM2
This variant has a Grpmax filtering allele frequency of 0.00001773 in gnomAD v4.1.0, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
Curation History
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