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.1623+3A>G

CA10587145

256598 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 4d08e15d-7c27-4174-9937-728646b86912
Approved on: 2025-09-26
Published on: 2025-09-26

HGVS expressions

NM_000545.8:c.1623+3A>G
NM_000545.8(HNF1A):c.1623+3A>G
NC_000012.12:g.120999392A>G
CM000674.2:g.120999392A>G
NC_000012.11:g.121437195A>G
CM000674.1:g.121437195A>G
NC_000012.10:g.119921578A>G
NG_011731.2:g.25647A>G
ENST00000560968.6:c.*370+3A>G
ENST00000257555.11:c.1623+3A>G
ENST00000257555.10:c.1623+3A>G
ENST00000540108.1:c.*1063+3A>G
ENST00000541395.5:c.1626A>G
ENST00000543427.5:c.1086+3A>G
ENST00000544413.2:c.1623+3A>G
ENST00000560968.5:c.1440+3A>G
ENST00000615446.4:c.411+3A>G
ENST00000617366.4:c.*32+3A>G
NM_000545.5:c.1623+3A>G
NM_000545.6:c.1623+3A>G
NM_001306179.1:c.1623+3A>G
NM_001306179.2:c.1623+3A>G
More

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 2
PS4 PP4

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.1623+3A>G variant in the HNF1 homeobox A gene, HNF1A, is predicted to remove a canonical splice donor site in intron 8 of NM_000545.8. Additionally, this variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.0 for donor loss, suggesting that the variant has no impact on splicing (BP4). This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because the number is below the ClinGen MDEP threshold (Clinvar ID: 256598; Internal lab contributors). Also, PP4 cannot be applied because, despite this variant being identified in an individual with diabetes, the MODY probability cannot be calculated as the age at diagnosis is above 35 years (Internal lab contributor). In summary, c.1623+3A>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): PM2_Supporting, BP4.
Met criteria codes
BP4
The computational splicing predictor SpliceAI gives a score of 0.00 for donor loss, suggesting that the variant has no impact on splicing (BP4).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
Not Met criteria codes
PS4
This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (Clinvar ID: 256598, Internal lab contributors).
PP4
This variant was identified in an individual with diabetes; however, the MODY probability cannot be calculated due to the age of diagnosis being over 35 (Internal lab contributors).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.