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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000545.6(HNF1A):c.1592G>C (p.Ser531Thr)

CA124484

14947 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4f7ac8c9-461a-4699-8865-f7a70c062ed4

HGVS expressions

NM_000545.6:c.1592G>C

NM_000545.6(HNF1A):c.1592G>C (p.Ser531Thr)

NC_000012.12:g.120999358G>C

CM000674.2:g.120999358G>C

NC_000012.11:g.121437161G>C

CM000674.1:g.121437161G>C

NC_000012.10:g.119921544G>C

NG_011731.2:g.25613G>C

ENST00000257555.11:c.1592G>C

ENST00000257555.10:c.1592G>C

ENST00000540108.1:c.*1032G>C

ENST00000541395.5:c.1592G>C

ENST00000543427.5:c.1055G>C

ENST00000544413.2:c.1592G>C

ENST00000560968.5:n.1409G>C

ENST00000615446.4:c.380G>C

ENST00000617366.4:c.*1G>C

NM_000545.5:c.1592G>C

NM_001306179.1:c.1592G>C

NM_000545.8:c.1592G>C

NM_001306179.2:c.1592G>C

NM_000545.8(HNF1A):c.1592G>C (p.Ser531Thr)

Uncertain Significance

BS4

PS4 PP3 PM2 BS1

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 Version 1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1592G>C variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of serine to threonine at codon 531 (p.(Ser531Thr)) of NM_000545.8. This variant does not segregate with diabetes in four families (BS4; internal lab contributors). In summary, c.1592G>C 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 1.1, approved 6/4/2021): BS4

BS4

This variant did not appear to segregate with disease in a family affected with diabetes mellitus.

PS4

PS4 cannot be used when variant does not meet PM2_Supporting.

PP3

REVEL score is not greater than 0.7 (actual value = 0.62).

PM2

This variant has an allele frequency in the European non-Finnish population greater than 0.00002 (actual value = 0.00004404).

BS1

This variant has a Popmax allele frequency less than 0.000033 (actual value = 0.00001687).

Approved on: 2021-12-31

Published on: 2022-07-11

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