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_000545.8(HNF1A):c.1383C>T (p.Pro461=)

CA6832031

435419 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7a30e9f6-0952-4d82-a4e0-d182ba4a1ed8

HGVS expressions

NM_000545.8:c.1383C>T

NM_000545.8(HNF1A):c.1383C>T (p.Pro461=)

NC_000012.12:g.120997547C>T

CM000674.2:g.120997547C>T

NC_000012.11:g.121435350C>T

CM000674.1:g.121435350C>T

NC_000012.10:g.119919733C>T

NG_011731.2:g.23802C>T

ENST00000257555.11:c.1383C>T

ENST00000257555.10:c.1383C>T

ENST00000400024.6:c.1383C>T

ENST00000402929.5:n.2249C>T

ENST00000535955.5:n.99C>T

ENST00000538626.2:n.247C>T

ENST00000538646.5:c.*359C>T

ENST00000540108.1:c.*823C>T

ENST00000541395.5:c.1383C>T

ENST00000541924.5:c.*397C>T

ENST00000543255.1:n.427C>T

ENST00000543427.5:c.846C>T

ENST00000544413.2:c.1383C>T

ENST00000544574.5:c.*146C>T

ENST00000560968.5:n.1200C>T

ENST00000615446.4:c.171C>T

ENST00000617366.4:c.587-87C>T

NM_000545.5:c.1383C>T

NM_000545.6:c.1383C>T

NM_001306179.1:c.1383C>T

NM_001306179.2:c.1383C>T

Likely Benign

BP7 BP5

PM2 BS1

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1383C>T variant in the HNF1 homeobox A gene, HNF1A, is a synonymous (silent) variant at codon 461 (p.(Pro461=)) of NM_000545.8. This variant was identified in a patient with an alternate molecular basis for disease (BP5; ClinVar: SCV000595127.1, personal communication from Genetic Services Laboratory, University of Chicago). Additionally, this synonymous variant is not predicted by SpliceAI to impact splicing (BP7). The variant frequency fell between the ClinGen MDEP BS1 and PM2_Supporting cutoffs; therefore, neither was applied. In summary, c.1383C>T meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): BP5, BP7.

BP7

This synonymous variant is not predicted by SpliceAI to impact splicing.

BP5

This variant was identified in a patient with an alternate molecular basis for disease (BP5; ClinVar: SCV000595127.1, personal communication from Genetic Services Laboratory, University of Chicago).

PM2

MAF in gnomAD ENF = 0.000026 > MDEP cutoff of 0.00002; one copy in AFR

BS1

Popmax Filtering AF = 0.000007070 < MDEP cutoff of 0.000033

Approved on: 2022-04-16

Published on: 2022-04-16

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.