NM_014585.6(SLC40A1):c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC (p.Lys422delinsValArgLeuThrArgThrValTer) AND Hemochromatosis type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 1, 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:: RCV001579308.2

Allele description [Variation Report for NM_014585.6(SLC40A1):c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC (p.Lys422delinsValArgLeuThrArgThrValTer)]

NM_014585.6(SLC40A1):c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC (p.Lys422delinsValArgLeuThrArgThrValTer)

Gene:

SLC40A1:solute carrier family 40 member 1 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_014585.6(SLC40A1):c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC (p.Lys422delinsValArgLeuThrArgThrValTer)

HGVS:

NC_000002.12:g.189563750_189563751insCAGGATTTGTGGCACCTTCTGACTGTCAAACTGTTCTTGTCAATCTCACGGTAGGTGTAATTGACTCTCCTTGAATG
NG_009027.1:g.22089_22090insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC
NM_014585.6:c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACCMANE SELECT
NP_055400.1:p.Lys422delinsValArgLeuThrArgThrValTer
LRG_837:g.22089_22090insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC
NC_000002.11:g.190428476_190428477insCAGGATTTGTGGCACCTTCTGACTGTCAAACTGTTCTTGTCAATCTCACGGTAGGTGTAATTGACTCTCCTTGAATG

Links:

dbSNP: rs2105620059

NCBI 1000 Genomes Browser:

rs2105620059

Molecular consequence:

NM_014585.6:c.1263_1264insGTGAGATTGACAAGAACAGTTTGACAGTCAGAAGGTGCCACAAATCCTGCATTCAAGGAGAGTCAATTACACCTACC - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

variation affecting protein structure [Variation Ontology: 0060]

Observations:

Condition(s)

Name:: Hemochromatosis type 4 (HFE4)
Synonyms:: Hemochromatosis, autosomal dominant; Hemochromatosis due to defect in ferroportin
Identifiers:: MONDO: MONDO:0011631; MedGen: C1853733; Orphanet: 139491; OMIM: 606069

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001805850	Human Genetics Unit, University Of Colombo	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 1, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16813613, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001805850

Human Genetics Unit, University Of Colombo

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 1, 2021)

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
Sri Lankan	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent.

Agarwal S, Sankar VH, Tewari D, Pradhan M.

Clin Genet. 2006 Jul;70(1):86-7. No abstract available.

PubMed [citation]

PMID:: 16813613

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 Human Genetics Unit, University Of Colombo, SCV001805850.1

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

Description

The p.Lys422fs variant in SLC40A1 has been reported in a Sri Lankan female with Beta Thalassaemia Major. This patient was transfusion-dependent with iron overload. Moreover, parents were carriers for Beta Thalassaemia (confirmed by HPLC).

#	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		1	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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