Variant: NM_175914.5:c.1306A>T

CA409110466

Gene: HNF4A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: 2349ea7a-33a0-47b7-a8e6-0a84e2fe2a35

HGVS expressions

NM_175914.5:c.1306A>T
NC_000020.11:g.44429612A>T
CM000682.2:g.44429612A>T
NC_000020.10:g.43058252A>T
CM000682.1:g.43058252A>T
NC_000020.9:g.42491666A>T
NG_009818.1:g.78812A>T
ENST00000316099.10:c.1372A>T
ENST00000316099.9:c.1372A>T
ENST00000316099.8:c.1372A>T
ENST00000316673.8:c.1306A>T
ENST00000372920.1:c.*1139A>T
ENST00000415691.2:c.1342A>T
ENST00000457232.5:c.1276A>T
ENST00000619550.4:c.1297A>T
NM_000457.4:c.1372A>T
NM_001030003.2:c.1276A>T
NM_001258355.1:c.1351A>T
NM_001287182.1:c.1267A>T
NM_001287183.1:c.1297A>T
NM_175914.4:c.1306A>T
NM_178849.2:c.1342A>T
NM_001030003.3:c.1276A>T
NM_001258355.2:c.1351A>T
NM_001287182.2:c.1267A>T
NM_178849.3:c.1342A>T
NM_000457.5:c.1372A>T
NM_000457.6:c.1372A>T
NM_001287183.2:c.1297A>T

Uncertain Significance

• Met criteria codes: PM2_Supporting PVS1_Supporting

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

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1306A>T variant in the hepatocyte nuclear factor-4-alpha gene, HNF4A, results in a premature termination at codon 436 (p.(Lys436Ter)) of NM_175914.4. This nonsense variant, located 3’ of codon 420 in exon 10 of 10, is not predicted to result in nonsense mediated decay of the transcript nor significantly disrupt the transactivation domain of the protein. There is insufficient clinical evidence that variants in this region lead to a monogenic diabetes phenotype. (PVS1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1306A>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 1.0.0, approved 11/16/2022): PVS1_Supporting, PM2_Supporting.

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PVS1_Supporting: This nonsense variant, located 3’ of codon 420 in exon 10 of 10, is not predicted to result in nonsense mediated decay of the transcript nor significantly disrupt the transactivation domain of the protein. There is insufficient clinical evidence that variants in this region lead to a monogenic diabetes phenotype. (PVS1_Supporting).

Approved on: 2023-05-27

Published on: 2023-05-27