VCV000011574.5 - ClinVar

NM_001271696.3(ABCB7):c.1200T>G (p.Ile400Met)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001271696.3(ABCB7):c.1200T>G (p.Ile400Met)

Variation ID: 11574 Accession: VCV000011574.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq13.3 X: 75071516 (GRCh38) [ NCBI UCSC ] X: 74291351 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 24, 2015	Jul 7, 2024	Nov 15, 2012

HGVS

Nucleotide	Protein	Molecular consequence
NM_001271696.3:c.1200T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001258625.1:p.Ile400Met	missense
NM_001271697.3:c.1080T>G	NP_001258626.1:p.Ile360Met	missense
NM_001271698.3:c.1122T>G	NP_001258627.1:p.Ile374Met	missense
NM_001271699.3:c.1083T>G	NP_001258628.1:p.Ile361Met	missense
NM_004299.6:c.1203T>G	NP_004290.2:p.Ile401Met	missense
NC_000023.11:g.75071516A>C
NC_000023.10:g.74291351A>C
NG_007980.3:g.89768T>G
LRG_1162:g.89768T>G
LRG_1162t1:c.1203T>G	LRG_1162p1:p.Ile401Met
LRG_1162t2:c.1200T>G	LRG_1162p2:p.Ile400Met

... more HGVS ... less HGVS

Protein change

I400M, I360M, I361M, I374M

Other names

p.I401M:ATT>ATG

Canonical SPDI

NC_000023.11:75071515:A:C

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA321819 OMIM: 300135.0001 dbSNP: rs72554634 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ABCB7		-	-	GRCh38 GRCh37	397	586

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
X-linked sideroblastic anemia with ataxia	Pathogenic (2)	no assertion criteria provided	May 1, 1999	RCV000012330.37
not provided	Pathogenic (1)	criteria provided, single submitter	Nov 15, 2012	RCV000197371.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 15, 2012) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not provided	GeneDx Accession: SCV000251007.11 First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015	Comment: show p.Ile401Met (ATT>ATG): c.1203 T>G in exon 9 of the ABCB7 gene (NM_004299.3). The I401M missense mutation in the ABCB7 gene has been reported previously in association with X-linked sideroblastic anemia in a family in which five male members were affected (Allikmets et al., 1999). In vitro studies using a yeast model found that the I401M mutation results in a partial loss of function of the yeast Atm1 protein (Allikmets et al., 1999). This result is consistent with a diagnosis of X-linked sideroblastic anemia. The variant is found in MITONUC-MITOP panel(s). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (May 01, 1999) N Not contributing to aggregate classification	no assertion criteria provided	SPINOCEREBELLAR ATAXIA, X-LINKED 6, WITH SIDEROBLASTIC ANEMIA	OMIM Accession: SCV000032564.3 First in ClinVar: Apr 04, 2013 Last updated: Jul 07, 2024	Publications: PubMed (2) PubMed: 10196363‚ 4045952 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In affected males from a family with X-linked spinocerebellar ataxia-6 with sideroblastic anemia (SCAX6; 301310), originally reported by Pagon et al. (1985), Allikmets et al. … (more) In affected males from a family with X-linked spinocerebellar ataxia-6 with sideroblastic anemia (SCAX6; 301310), originally reported by Pagon et al. (1985), Allikmets et al. (1999) identified a hemizygous ile400-to-met (I400M) mutation in the ABCB7 gene. The mutation, which occurred in a predicted transmembrane segment of the protein, was found to segregate with the disease in the family. The mutation was not detected in at least 600 chromosomes of general population controls. Introduction of the corresponding mutation into the orthologous Saccharomyces cerevisiae gene resulted in a partial loss of function of the yeast ATM1 protein. In addition, the human wildtype ABCB7 protein was able to complement ATM1 deletion in yeast. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	X-linked sideroblastic anemia with ataxia	GeneReviews Accession: SCV000148003.3 First in ClinVar: Apr 27, 2014 Last updated: Oct 01, 2022	Publications: PubMed (1) PubMed: 10196363 Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes Observation 1 Collection method: literature only Allele origin: germline Affected status: yes

Comment:

p.Ile401Met (ATT>ATG): c.1203 T>G in exon 9 of the ABCB7 gene (NM_004299.3). The I401M missense mutation in the ABCB7 gene has been reported previously in association with X-linked sideroblastic anemia in a family in which five male members were affected (Allikmets et al., 1999). In vitro studies using a yeast model found that the I401M mutation results in a partial loss of function of the yeast Atm1 protein (Allikmets et al., 1999). This result is consistent with a diagnosis of X-linked sideroblastic anemia. The variant is found in MITONUC-MITOP panel(s).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY.	Adam MP	-	2014	PMID: 20301496
Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A).	Allikmets R	Human molecular genetics	1999	PMID: 10196363
Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.	Pagon RA	Journal of medical genetics	1985	PMID: 4045952

Text-mined citations for rs72554634 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 04, 2026