NM_000410.4(HFE):c.50C>T (p.Thr17Ile) AND Hereditary hemochromatosis

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 20, 2022
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:: RCV000538099.5

Allele description

NM_000410.4(HFE):c.50C>T (p.Thr17Ile)

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.50C>T (p.Thr17Ile)

HGVS:

NC_000006.12:g.26087490C>T
NG_008720.2:g.5210C>T
NM_000410.4:c.50C>TMANE SELECT
NM_001300749.3:c.50C>T
NM_001384164.1:c.50C>T
NM_001406751.1:c.50C>T
NM_001406752.1:c.50C>T
NM_139003.3:c.50C>T
NM_139004.3:c.50C>T
NM_139006.3:c.50C>T
NM_139007.3:c.50C>T
NM_139008.3:c.50C>T
NM_139009.3:c.50C>T
NM_139010.3:c.50C>T
NM_139011.3:c.50C>T
NP_000401.1:p.Thr17Ile
NP_000401.1:p.Thr17Ile
NP_001287678.1:p.Thr17Ile
NP_001287678.1:p.Thr17Ile
NP_001371093.1:p.Thr17Ile
NP_001393680.1:p.Thr17Ile
NP_001393681.1:p.Thr17Ile
NP_620572.1:p.Thr17Ile
NP_620573.1:p.Thr17Ile
NP_620575.1:p.Thr17Ile
NP_620576.1:p.Thr17Ile
NP_620577.1:p.Thr17Ile
NP_620578.1:p.Thr17Ile
NP_620579.1:p.Thr17Ile
NP_620580.1:p.Thr17Ile
LRG_748t1:c.50C>T
LRG_748:g.5210C>T
LRG_748p1:p.Thr17Ile
NC_000006.11:g.26087718C>T
NM_000410.3:c.50C>T
NM_001300749.2:c.50C>T
NR_144383.1:n.985G>A

Protein change:

T17I

Links:

dbSNP: rs143662783

NCBI 1000 Genomes Browser:

rs143662783

Molecular consequence:

NM_000410.4:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001300749.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384164.1:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406751.1:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406752.1:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139003.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139004.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139006.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139007.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139008.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139009.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139010.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139011.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_144383.1:n.985G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary hemochromatosis (HFE)
Identifiers:: MONDO: MONDO:0006507; MedGen: C0392514; OMIM: PS235200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000633734	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26151776, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000633734

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 20, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Next-generation sequencing: Application of a novel platform to analyze atypical iron disorders.

McDonald CJ, Ostini L, Wallace DF, Lyons A, Crawford DH, Subramaniam VN.

J Hepatol. 2015 Nov;63(5):1288-93. doi: 10.1016/j.jhep.2015.06.027. Epub 2015 Jul 4. Review.

PubMed [citation]

PMID:: 26151776

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 Invitae, SCV000633734.3

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 17 of the HFE protein (p.Thr17Ile). This variant is present in population databases (rs143662783, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with iron overload (PMID: 26151776). ClinVar contains an entry for this variant (Variation ID: 461193). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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: Mar 30, 2024

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