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 computer assertion could be determined for this classification!


Variant: NM_000545.8(HNF1A):c.1135C>T (p.Pro379Ser)

CA6831956

2052397 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 29442a09-a120-4693-a83d-50210bc7797b
Approved on: 2024-08-01
Published on: 2024-08-01

HGVS expressions

NM_000545.8:c.1135C>T
NM_000545.8(HNF1A):c.1135C>T (p.Pro379Ser)
NC_000012.12:g.120996568C>T
CM000674.2:g.120996568C>T
NC_000012.11:g.121434371C>T
CM000674.1:g.121434371C>T
NC_000012.10:g.119918754C>T
NG_011731.2:g.22823C>T
ENST00000560968.6:c.809C>T
ENST00000257555.11:c.1135C>T
ENST00000257555.10:c.1135C>T
ENST00000400024.6:c.1135C>T
ENST00000402929.5:n.1270C>T
ENST00000535955.5:n.43-923C>T
ENST00000538626.2:n.191-923C>T
ENST00000538646.5:c.*111C>T
ENST00000540108.1:c.*575C>T
ENST00000541395.5:c.1135C>T
ENST00000541924.5:c.*149C>T
ENST00000543255.1:n.179C>T
ENST00000543427.5:c.634-36C>T
ENST00000544413.2:c.1135C>T
ENST00000544574.5:c.73-49C>T
ENST00000560968.5:c.952C>T
ENST00000615446.4:c.-78C>T
ENST00000617366.4:c.587-1066C>T
NM_000545.5:c.1135C>T
NM_000545.6:c.1135C>T
NM_001306179.1:c.1135C>T
NM_001306179.2:c.1135C>T
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Benign

Met criteria codes 3
BA1 PP3 BP2
Not Met criteria codes 1
PS4

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 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1135C>T variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to serine at codon 379 (p.(Pro379Ser)) of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.0001567, which is greater than the MDEP threshold for BA1 (0.0001)(BA1). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.967, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant has been observed in unknown phase with the variant c.872dup, p.Gly292Argfs*25 (internal lab contributors), which is classified as pathogenic by the ClinGen MDEP (BP2). This variant was identified in at least 4 unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because the variant does not meet the PM2_Supporting cutoff (PMID 18003757, internal lab contributors). In summary, c.1135C>T meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/2023): BA1, BP2, PP3.
Met criteria codes
BA1
This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.0001567, which is greater than the MDEP threshold for BA1 (0.0001)(BA1)
PP3
This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.967, which is greater than the MDEP VCEP threshold of 0.70 (PP3).
BP2
This variant has been observed in unknown phase with the variant c.872dup, p.Gly292Argfs*25 (internal lab contributors), which is classified as pathogenic by the ClinGen MDEP (BP2).
Not Met criteria codes
PS4
This variant was identified in at least 4 unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because the variant does not meet the PM2_Supporting cutoff (PMID 18003757, internal lab contributors).
Curation History
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