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

Germline classification:
Likely benign (1 submission)
Last evaluated:
May 27, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003234542.3

Allele description [Variation Report for NM_175914.5(HNF4A):c.361A>G (p.Ser121Gly)]

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

Gene:
HNF4A:hepatocyte nuclear factor 4 alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.12
Genomic location:
Preferred name:
NM_175914.5(HNF4A):c.361A>G (p.Ser121Gly)
Other names:
NM_175914.5(HNF4A):c.361A>G; p.Ser121Gly
HGVS:
  • NC_000020.11:g.44413735A>G
  • NG_009818.1:g.62935A>G
  • NM_000457.6: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_001287183.2:c.352A>G
  • NM_001287184.2:c.352A>G
  • NM_175914.5:c.361A>GMANE SELECT
  • NM_178849.3:c.427A>G
  • NM_178850.3:c.427A>G
  • NP_000448.3:p.Ser143Gly
  • NP_000448.3:p.Ser143Gly
  • NP_001025174.1:p.Ser121Gly
  • NP_001025175.1:p.Ser121Gly
  • NP_001245284.1:p.Ser136Gly
  • NP_001274111.1:p.Ser118Gly
  • NP_001274112.1:p.Ser118Gly
  • NP_001274113.1:p.Ser118Gly
  • NP_787110.2:p.Ser121Gly
  • NP_849180.1:p.Ser143Gly
  • NP_849181.1:p.Ser143Gly
  • LRG_483t1:c.361A>G
  • LRG_483t2:c.427A>G
  • LRG_483:g.62935A>G
  • LRG_483p2:p.Ser143Gly
  • NC_000020.10:g.43042375A>G
  • NM_000457.3:c.427A>G
  • NM_000457.4(HNF4A):c.427A>G
  • NM_000457.4:c.427A>G
  • NM_175914.3:c.361A>G
  • NM_175914.4:c.361A>G
Protein change:
S118G
Links:
dbSNP: rs193922472
NCBI 1000 Genomes Browser:
rs193922472
Molecular consequence:
  • NM_000457.6:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030003.3:c.361A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030004.3:c.361A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258355.2:c.406A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287182.2:c.352A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287183.2:c.352A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287184.2:c.352A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_175914.5:c.361A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178849.3:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178850.3:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Monogenic diabetes
Identifiers:
MONDO: MONDO:0015967; MedGen: C3888631

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003932650ClinGen Monogenic Diabetes Variant Curation Expert Panel
reviewed by expert panel

(MDEP HNF4A Specificiations 1.0.0)		Likely benign
(May 27, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Monogenic Diabetes Variant Curation Expert Panel, SCV003932650.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024