NM_000410.4(HFE):c.18G>C (p.Arg6Ser) AND Hemochromatosis type 1

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000199898.11

Allele description [Variation Report for NM_000410.4(HFE):c.18G>C (p.Arg6Ser)]

NM_000410.4(HFE):c.18G>C (p.Arg6Ser)

Genes:

HFE-AS1:HFE antisense RNA 1 [Gene - HGNC]
HFE:homeostatic iron regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.2

Genomic location:

Preferred name:

NM_000410.4(HFE):c.18G>C (p.Arg6Ser)

Other names:

NM_000410.3(HFE):c.18G>C(p.Arg6Ser); NM_001300749.1(HFE):c.18G>C(p.Arg6Ser); NM_139003.2(HFE):c.18G>C(p.Arg6Ser); NM_139004.2(HFE):c.18G>C(p.Arg6Ser); NM_139006.2(HFE):c.18G>C(p.Arg6Ser); NM_139007.2(HFE):c.18G>C(p.Arg6Ser); NM_139008.2(HFE):c.18G>C(p.Arg6Ser); NM_139009.2(HFE):c.18G>C(p.Arg6Ser); NM_139010.2(HFE):c.18G>C(p.Arg6Ser); NM_139011.2(HFE):c.18G>C(p.Arg6Ser)

HGVS:

NC_000006.12:g.26087458G>C
NG_008720.2:g.5178G>C
NM_000410.4:c.18G>CMANE SELECT
NM_001300749.3:c.18G>C
NM_001384164.1:c.18G>C
NM_001406751.1:c.18G>C
NM_001406752.1:c.18G>C
NM_139003.3:c.18G>C
NM_139004.3:c.18G>C
NM_139006.3:c.18G>C
NM_139007.3:c.18G>C
NM_139008.3:c.18G>C
NM_139009.3:c.18G>C
NM_139010.3:c.18G>C
NM_139011.3:c.18G>C
NP_000401.1:p.Arg6Ser
NP_000401.1:p.Arg6Ser
NP_001287678.1:p.Arg6Ser
NP_001287678.1:p.Arg6Ser
NP_001371093.1:p.Arg6Ser
NP_001393680.1:p.Arg6Ser
NP_001393681.1:p.Arg6Ser
NP_620572.1:p.Arg6Ser
NP_620573.1:p.Arg6Ser
NP_620575.1:p.Arg6Ser
NP_620576.1:p.Arg6Ser
NP_620577.1:p.Arg6Ser
NP_620578.1:p.Arg6Ser
NP_620579.1:p.Arg6Ser
NP_620580.1:p.Arg6Ser
LRG_748t1:c.18G>C
LRG_748:g.5178G>C
LRG_748p1:p.Arg6Ser
NC_000006.11:g.26087686G>C
NC_000006.11:g.26087686G>C
NM_000410.3:c.18G>C
NM_001300749.2:c.18G>C
NR_144383.1:n.1017C>G
Q30201:p.Arg6Ser

Protein change:

R6S

Links:

UniProtKB: Q30201#VAR_042506; dbSNP: rs149342416

NCBI 1000 Genomes Browser:

rs149342416

Molecular consequence:

NM_000410.4:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300749.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384164.1:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406751.1:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406752.1:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139003.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139004.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139006.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139007.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139008.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139009.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139010.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139011.3:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_144383.1:n.1017C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hemochromatosis type 1 (HFE1)
Synonyms:: HFE-Associated Hereditary Hemochromatosis
Identifiers:: MONDO: MONDO:0021001; MedGen: C3469186; OMIM: 235200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000803526	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 31, 2018)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV001317550	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12584229, 15350019 Citation Link,
SCV003801715	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000803526

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 31, 2018)

unknown

curation

PubMed (1)
[See all records that cite this PMID]

SCV001317550

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV003801715

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation.

Wigg AJ, Harley H, Casey G.

Gut. 2003 Mar;52(3):433-5.

PubMed [citation]

PMID:: 12584229
PMCID:: PMC1773567

Can liver transplantation improve our understanding of the pathophysiology of iron overload?

Brandhagen D.

Liver Transpl. 2004 Sep;10(9):1218-20. No abstract available.

PubMed [citation]

PMID:: 15350019

See all PubMed Citations (3)

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000803526.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Hemochromatosis, type 1, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.).

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

From Illumina Laboratory Services, Illumina, SCV001317550.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Genome-Nilou Lab, SCV003801715.1

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

#	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: Apr 15, 2024

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