Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000545.6(HNF1A):c.1114G>A (p.Ala372Thr)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA231160

129226 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8dabb95c-a145-4927-a396-88fc75ed3ca5

Approved on: 2025-04-11

Published on: 2025-06-09

HGVS expressions

NM_000545.6:c.1114G>A

NM_000545.6(HNF1A):c.1114G>A (p.Ala372Thr)

NC_000012.12:g.120996547G>A

CM000674.2:g.120996547G>A

NC_000012.11:g.121434350G>A

CM000674.1:g.121434350G>A

NC_000012.10:g.119918733G>A

NG_011731.2:g.22802G>A

ENST00000560968.6:c.788G>A

ENST00000257555.11:c.1114G>A

ENST00000257555.10:c.1114G>A

ENST00000400024.6:c.1114G>A

ENST00000402929.5:n.1249G>A

ENST00000535955.5:n.43-944G>A

ENST00000538626.2:n.191-944G>A

ENST00000538646.5:c.*90G>A

ENST00000540108.1:c.*554G>A

ENST00000541395.5:c.1114G>A

ENST00000541924.5:c.*128G>A

ENST00000543255.1:n.158G>A

ENST00000543427.5:c.634-57G>A

ENST00000544413.2:c.1114G>A

ENST00000544574.5:c.73-70G>A

ENST00000560968.5:c.931G>A

ENST00000615446.4:c.-99G>A

ENST00000617366.4:c.587-1087G>A

NM_000545.5:c.1114G>A

NM_001306179.1:c.1114G>A

NM_000545.8:c.1114G>A

NM_001306179.2:c.1114G>A

Uncertain Significance

PM2

PP3 BP4

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1114G>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of alanine to threonine at codon 372 (p.(Ala372Thr)) of NM_000545.8. This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). This variant has a REVEL score of 0.371, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function. In summary, c.1114G>A 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 2.1.0, approved 8/11/23): PM2_Supporting.

PM2

This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting).

PP3

This variant has a REVEL score of 0.371, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function.

BP4

This variant has a REVEL score of 0.371, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function.

Curation History

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