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_000545.8(HNF1A):c.1896A>G (p.Ter632=)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA160007

134507 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 852554e9-0b0e-4bb4-a8a2-36100b94e3b1

Approved on: 2025-09-02

Published on: 2025-09-02

HGVS expressions

NM_000545.8:c.1896A>G

NM_000545.8(HNF1A):c.1896A>G (p.Ter632=)

NC_000012.12:g.121001192A>G

CM000674.2:g.121001192A>G

NC_000012.11:g.121438995A>G

CM000674.1:g.121438995A>G

NC_000012.10:g.119923378A>G

NG_011731.2:g.27447A>G

ENST00000560968.6:c.*643A>G

ENST00000257555.11:c.1896A>G

ENST00000257555.10:c.1896A>G

ENST00000288757.7:c.*2961T>C

ENST00000540108.1:c.*1336A>G

ENST00000541395.5:c.1989A>G

ENST00000543427.5:c.1359A>G

ENST00000544413.2:c.1917A>G

ENST00000560968.5:c.1713A>G

ENST00000615446.4:c.684A>G

ENST00000617366.4:c.*305A>G

NM_000545.5:c.1896A>G

NM_000545.6:c.1896A>G

NM_001306179.1:c.1917A>G

NM_001286191.2:c.*2961T>C

NM_001286196.2:c.*2961T>C

NM_001306179.2:c.1917A>G

NM_022895.3:c.*2961T>C

Uncertain Significance

BP4 PM2_Supporting

BS1 BP7

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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1896A>G variant in the HNF1 homeobox A gene, HNF1A, is a synonymous (silent) variant at codon 632 (p.Ter632=) of NM_000545.8. The computational splicing predictor SpliceAI gives a score of 0.01 for acceptor loss/gain, suggesting that the variant has no impact on splicing (BP4). However, BP7 was not applied for this synonymous variant because phyloP100way suggests conservation with a score >2.0 (2.801). This variant has a gnomAD v4.1.0 Grpmax filtering allele frequency of 0.00000247, which is below the ClinGen MDEP threshold of 0.000003 (PM2_Supporting). In summary, c.1896A>G 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 3.0.0, approved 6/30/2025): BP4, PM2_Supporting.

BP4

The computational splicing predictor SpliceAI gives a score of 0.01 for acceptor loss/gain, suggesting that the variant has no impact on splicing (BP4).

PM2_Supporting

This variant has a gnomAD v4.1.0 Grpmax filtering allele frequency of 0.00000247, which is below the ClinGen MDEP threshold of 0.000003 (PM2_Supporting).

BS1

Popmax AF = 0.000007050 < 0.000033

BP7

BP7 was not applied for this synonymous variant because phyloP100way suggests conservation with a score >2.0 (2.801).

Curation History

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