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_175914.5(HNF4A):c.361A>G (p.Ser121Gly)

CA213929

36349 (ClinVar)

Gene: HNF4A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ec9dabe5-43cc-47cd-b13c-02d6f5fba963

HGVS expressions

NM_175914.5:c.361A>G

NM_175914.5(HNF4A):c.361A>G (p.Ser121Gly)

NC_000020.11:g.44413735A>G

CM000682.2:g.44413735A>G

NC_000020.10:g.43042375A>G

CM000682.1:g.43042375A>G

NC_000020.9:g.42475789A>G

NG_009818.1:g.62935A>G

ENST00000316099.10:c.427A>G

ENST00000619550.5:n.401A>G

ENST00000683148.1:n.403A>G

ENST00000683657.1:n.1551A>G

ENST00000316099.9:c.427A>G

ENST00000316099.8:c.427A>G

ENST00000316673.8:c.361A>G

ENST00000372920.1:c.*194A>G

ENST00000415691.2:c.427A>G

ENST00000443598.6:c.427A>G

ENST00000457232.5:c.361A>G

ENST00000609795.5:c.361A>G

ENST00000619550.4:c.352A>G

NM_000457.4:c.427A>G

NM_001030003.2:c.361A>G

NM_001030004.2:c.361A>G

NM_001258355.1:c.406A>G

NM_001287182.1:c.352A>G

NM_001287183.1:c.352A>G

NM_001287184.1:c.352A>G

NM_175914.4:c.361A>G

NM_178849.2:c.427A>G

NM_178850.2:c.427A>G

NM_001030003.3:c.361A>G

NM_001030004.3:c.361A>G

NM_001258355.2:c.406A>G

NM_001287182.2:c.352A>G

NM_001287184.2:c.352A>G

NM_178849.3:c.427A>G

NM_178850.3:c.427A>G

NM_000457.5:c.427A>G

NM_000457.6:c.427A>G

NM_001287183.2:c.352A>G

Likely Benign

BP5 BS1

BP4 PP3

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 HNF4A Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.361A>G variant in the hepatocyte nuclear factor-4 alpha gene, HNF4A, causes an amino acid change of serine to glycine at codon 121 (p.(Ser121Gly)) in NM_175914.5. The Popmax filtering allele frequency of the c.361A>G variant in gnomAD v2.1.1 is 0.00006673, which is greater than the MDEP threshold for BS1 (0.000033) (BS1). This variant has a REVEL score of 0.555, which is between the ClinGen MDEP established cutoffs for PP3 and BS4, predicting neither a damaging nor benign impact on HNF4A function; thus, neither criterion will be applied. This variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). In summary, c.361A>G meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.0.0, approved 11/16/2022): BS1, BP5.

BP5

This variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors).

BS1

The Popmax filtering allele frequency of the c.361A>G variant in gnomAD v2.1.1 is 0.00006673, which is greater than the MDEP threshold for BS1 (0.000033) (BS1).

BP4

This variant has a REVEL score of 0.555, which is between the ClinGen MDEP established cutoffs for PP3 and BS4, predicting neither a damaging nor benign impact on HNF4A function; thus, neither criterion will be applied.

PP3

Approved on: 2023-05-27

Published on: 2023-05-27

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