NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 16, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001796486.5

Allele description [Variation Report for NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln)]

NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln)

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.353G>A (p.Arg118Gln)

HGVS:

NC_000020.11:g.44413727G>A
NG_009818.1:g.62927G>A
NM_000457.6:c.419G>A
NM_001030003.3:c.353G>A
NM_001030004.3:c.353G>A
NM_001258355.2:c.398G>A
NM_001287182.2:c.344G>A
NM_001287183.2:c.344G>A
NM_001287184.2:c.344G>A
NM_175914.5:c.353G>AMANE SELECT
NM_178849.3:c.419G>A
NM_178850.3:c.419G>A
NP_000448.3:p.Arg140Gln
NP_001025174.1:p.Arg118Gln
NP_001025175.1:p.Arg118Gln
NP_001245284.1:p.Arg133Gln
NP_001274111.1:p.Arg115Gln
NP_001274112.1:p.Arg115Gln
NP_001274113.1:p.Arg115Gln
NP_787110.2:p.Arg118Gln
NP_787110.2:p.Arg118Gln
NP_849180.1:p.Arg140Gln
NP_849181.1:p.Arg140Gln
LRG_483t1:c.353G>A
LRG_483:g.62927G>A
LRG_483p1:p.Arg118Gln
NC_000020.10:g.43042367G>A
NM_175914.4:c.353G>A

Protein change:

R115Q

Links:

dbSNP: rs764196059

NCBI 1000 Genomes Browser:

rs764196059

Molecular consequence:

NM_000457.6:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001030003.3:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001030004.3:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258355.2:c.398G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287182.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287183.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287184.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_175914.5:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178849.3:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178850.3:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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hypothetical protein M876_01130 [Elizabethkingia anophelis FMS-007]
hypothetical protein M876_01130 [Elizabethkingia anophelis FMS-007]
gi|822870945|gnl|PRJNA210135|M876_0 gb|AKH93169.1|

Protein
LOC126593231 [Malus sylvestris]
LOC126593231 [Malus sylvestris]
Gene ID:126593231

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002036120	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002037420	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV004273848	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25555642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002036120

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV002037420

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV004273848

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular genetic testing of patients with monogenic diabetes and hyperinsulinism.

Bennett JT, Vasta V, Zhang M, Narayanan J, Gerrits P, Hahn SH.

Mol Genet Metab. 2015 Mar;114(3):451-8. doi: 10.1016/j.ymgme.2014.12.304. Epub 2014 Dec 20.

PubMed [citation]

PMID:: 25555642
PMCID:: PMC7852340

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV002036120.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV002037420.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004273848.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense change has been observed in individual(s) with clinical features of maturity onset diabetes of the young (PMID: 25555642; Invitae). This variant is present in population databases (rs764196059, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 118 of the HNF4A protein (p.Arg118Gln). ClinVar contains an entry for this variant (Variation ID: 1098751). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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