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.1548C>T (p.Gly516=)

CA10587144

256597 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 09564224-5807-4d6b-b8dc-ce4a211ca180
Approved on: 2025-10-03
Published on: 2025-10-03

HGVS expressions

NM_000545.8:c.1548C>T
NM_000545.8(HNF1A):c.1548C>T (p.Gly516=)
NC_000012.12:g.120999314C>T
CM000674.2:g.120999314C>T
NC_000012.11:g.121437117C>T
CM000674.1:g.121437117C>T
NC_000012.10:g.119921500C>T
NG_011731.2:g.25569C>T
ENST00000560968.6:c.*295C>T
ENST00000257555.11:c.1548C>T
ENST00000257555.10:c.1548C>T
ENST00000540108.1:c.*988C>T
ENST00000541395.5:c.1548C>T
ENST00000543427.5:c.1011C>T
ENST00000544413.2:c.1548C>T
ENST00000560968.5:c.1365C>T
ENST00000615446.4:c.336C>T
ENST00000617366.4:c.665C>T
NM_000545.5:c.1548C>T
NM_000545.6:c.1548C>T
NM_001306179.1:c.1548C>T
NM_001306179.2:c.1548C>T
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Uncertain Significance

Met criteria codes 2
PP3 PM2_Supporting
Not Met criteria codes 2
BP7 BP4

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 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1548C>T variant in the HNF1 homeobox A gene, HNF1A, is a synonymous (silent) variant at codon 516 (p.(Gly516=)) of NM_000545.8. This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to only one copy in any subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.47 for splice acceptor gain, predicting that the variant impacts the acceptor site of intron 7 of HNF1A (PP3). In summary, c.1548C>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 3.0.0, approved 6/30/2025): PM2_Supporting, PP3.
Met criteria codes
PP3
The computational splicing predictor SpliceAI gives a score of 0.47 for splice acceptor gain, suggesting that the variant impacts splicing (PP3).
PM2_Supporting
This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to only one copy in any subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (PM2_Supporting).
Not Met criteria codes
BP7
BP7 was not applied for this synonymous variant because SpliceAI predicts an impact on splicing. The phyloP100way score of 0.948 does not predicts conservation.
BP4
BP4 was not applied to this synonymous variant since the computational splice predictor SpliceAI gives a score of 0.47 for splice acceptor gain, suggesting an impact on splicing.
Curation History
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