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NM_000410.4(HFE):c.193A>T (p.Ser65Cys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 30, 2021
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:
RCV003224085.8

Allele description [Variation Report for NM_000410.4(HFE):c.193A>T (p.Ser65Cys)]

NM_000410.4(HFE):c.193A>T (p.Ser65Cys)

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.193A>T (p.Ser65Cys)
HGVS:
  • NC_000006.12:g.26090957A>T
  • NG_008720.2:g.8677A>T
  • NM_000410.4:c.193A>TMANE SELECT
  • NM_001300749.3:c.193A>T
  • NM_001384164.1:c.193A>T
  • NM_001406751.1:c.193A>T
  • NM_139003.3:c.193A>T
  • NM_139004.3:c.193A>T
  • NM_139006.3:c.193A>T
  • NM_139007.3:c.77-357A>T
  • NM_139008.3:c.77-357A>T
  • NM_139009.3:c.124A>T
  • NM_139010.3:c.77-1728A>T
  • NM_139011.3:c.77-2162A>T
  • NP_000401.1:p.Ser65Cys
  • NP_000401.1:p.Ser65Cys
  • NP_000401.1:p.Ser65Cys
  • NP_001287678.1:p.Ser65Cys
  • NP_001287678.1:p.Ser65Cys
  • NP_001371093.1:p.Ser65Cys
  • NP_001393680.1:p.Ser65Cys
  • NP_620572.1:p.Ser65Cys
  • NP_620573.1:p.Ser65Cys
  • NP_620575.1:p.Ser65Cys
  • NP_620578.1:p.Ser42Cys
  • LRG_748t1:c.193A>T
  • LRG_748:g.8677A>T
  • LRG_748p1:p.Ser65Cys
  • NC_000006.11:g.26091185A>T
  • NM_000410.3:c.193A>T
  • NM_001300749.2:c.193A>T
  • NR_144383.1:n.78T>A
  • Q30201:p.Ser65Cys
Protein change:
S42C; SER65CYS
Links:
Genetic Testing Registry (GTR): GTR000321635; UniProtKB: Q30201#VAR_004397; OMIM: 613609.0003; dbSNP: rs1800730
NCBI 1000 Genomes Browser:
rs1800730
Molecular consequence:
  • NM_139007.3:c.77-357A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139008.3:c.77-357A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139010.3:c.77-1728A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139011.3:c.77-2162A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000410.4:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001300749.3:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384164.1:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406751.1:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139003.3:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139004.3:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139006.3:c.193A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139009.3:c.124A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_144383.1:n.78T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Variegate porphyria (VP)
Synonyms:
Porphyria, South African type; Protoporphyrinogen oxidase deficiency; PPOX deficiency
Identifiers:
MONDO: MONDO:0008297; MedGen: C0162532; Orphanet: 79473; OMIM: 176200
Name:
Microvascular complications of diabetes, susceptibility to, 7
Synonyms:
Microvascular complications of diabetes 7
Identifiers:
MONDO: MONDO:0012971; MedGen: C2673520; OMIM: 612635
Name:
Alzheimer disease type 1 (AD1)
Synonyms:
ALZHEIMER DISEASE, FAMILIAL, 1; ALZHEIMER DISEASE, FAMILIAL, 1, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0007088; MedGen: C1863052; OMIM: 104300
Name:
Hemochromatosis type 1 (HFE1)
Synonyms:
HFE-Associated Hereditary Hemochromatosis
Identifiers:
MONDO: MONDO:0021001; MedGen: C3469186; OMIM: 235200
Name:
Transferrin serum level quantitative trait locus 2 (TFQTL2)
Identifiers:
MedGen: C3280096; OMIM: 614193
Name:
Familial porphyria cutanea tarda (PCT)
Synonyms:
PCT, TYPE II; PORPHYRIA CUTANEA TARDA, TYPE II; PORPHYRIA, HEPATOCUTANEOUS TYPE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008296; MedGen: C0268323; Orphanet: 101330; OMIM: 176100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003920031Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 30, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920031.1

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

Description

HFE NM_000410.3 exon 2 p.Ser65Cys (c.193A>T): This variant has been reported in the literature in the heterozygous or compound heterozygous state in several individuals with hemochromatosis and is reported to be enriched in this population compared to controls (Mura 1999 PMID:10194428, Holstrom 2002 PMID:12377814). However, additional studies did not find this association (Arya 1999 PMID:10660483, Pendersen 2009 PMID:19159930). Some authors suggest that this variant may act as a risk allele or low penetrance variant when in trans with the Cys282Tyr or His63Asp variants (Wallace 2002 PMID:11943417, Le Gac 2005 PMID:16132052). This variant is also present in 1% (2891/282878) of total alleles in the Genome Aggregation Database, including 24 homozygotes (https://gnomad.broadinstitute.org/variant/6-26091185-A-T). This variant is present in ClinVar (Variation ID:11). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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

Last Updated: Oct 26, 2024