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NM_000410.4(HFE):c.498G>C (p.Lys166Asn) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 23, 2024
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:
RCV004690170.1

Allele description [Variation Report for NM_000410.4(HFE):c.498G>C (p.Lys166Asn)]

NM_000410.4(HFE):c.498G>C (p.Lys166Asn)

Gene:
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.498G>C (p.Lys166Asn)
HGVS:
  • NC_000006.12:g.26091471G>C
  • NG_008720.2:g.9191G>C
  • NM_000410.4:c.498G>CMANE SELECT
  • NM_001300749.3:c.498G>C
  • NM_001384164.1:c.498G>C
  • NM_001406751.1:c.498G>C
  • NM_001406752.1:c.234G>C
  • NM_139003.3:c.340+367G>C
  • NM_139004.3:c.340+367G>C
  • NM_139006.3:c.498G>C
  • NM_139007.3:c.234G>C
  • NM_139008.3:c.234G>C
  • NM_139009.3:c.429G>C
  • NM_139010.3:c.77-1214G>C
  • NM_139011.3:c.77-1648G>C
  • NP_000401.1:p.Lys166Asn
  • NP_000401.1:p.Lys166Asn
  • NP_001287678.1:p.Lys166Asn
  • NP_001287678.1:p.Lys166Asn
  • NP_001371093.1:p.Lys166Asn
  • NP_001393680.1:p.Lys166Asn
  • NP_001393681.1:p.Lys78Asn
  • NP_620575.1:p.Lys166Asn
  • NP_620576.1:p.Lys78Asn
  • NP_620577.1:p.Lys78Asn
  • NP_620578.1:p.Lys143Asn
  • LRG_748t1:c.498G>C
  • LRG_748:g.9191G>C
  • LRG_748p1:p.Lys166Asn
  • NC_000006.11:g.26091699G>C
  • NM_000410.3:c.498G>C
  • NM_001300749.2:c.498G>C
Protein change:
K143N
Links:
dbSNP: rs753179816
NCBI 1000 Genomes Browser:
rs753179816
Molecular consequence:
  • NM_139003.3:c.340+367G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139004.3:c.340+367G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139010.3:c.77-1214G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139011.3:c.77-1648G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000410.4:c.498G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001300749.3:c.498G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384164.1:c.498G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406751.1:c.498G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406752.1:c.234G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139006.3:c.498G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139007.3:c.234G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139008.3:c.234G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139009.3:c.429G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005184992Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(May 23, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

Hamdi-Rozé H, Beaumont-Epinette MP, Ben Ali Z, Le Lan C, Loustaud-Ratti V, Causse X, Loreal O, Deugnier Y, Brissot P, Jouanolle AM, Bardou-Jacquet E.

Am J Hematol. 2016 Dec;91(12):1202-1205. doi: 10.1002/ajh.24535. Epub 2016 Aug 22.

PubMed [citation]
PMID:
27518069

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005184992.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: HFE c.498G>C (p.Lys166Asn) results in a non-conservative amino acid change located in the MHC class I-like antigen recognition-like domain (IPR011161) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.498G>C has been reported in the literature in at least one compound heterozygous individual affected with hemochromatosis (e.g., Hamdi-Roze_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27518069). ClinVar contains an entry for this variant (Variation ID: 1409845). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Sep 29, 2024