NM_004134.7(HSPA9):c.1373_1378del (p.Ile458_Asn459del) AND Autosomal dominant sideroblastic anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 12, 2017
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000209862.4

Allele description [Variation Report for NM_004134.7(HSPA9):c.1373_1378del (p.Ile458_Asn459del)]

NM_004134.7(HSPA9):c.1373_1378del (p.Ile458_Asn459del)

Gene:

HSPA9:heat shock protein family A (Hsp70) member 9 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_004134.7(HSPA9):c.1373_1378del (p.Ile458_Asn459del)

HGVS:

NC_000005.10:g.138559898_138559903del
NG_029469.1:g.20729_20734del
NM_004134.7:c.1373_1378delMANE SELECT
NP_004125.3:p.Ile458_Asn459del
LRG_1344t1:c.1373_1378del
LRG_1344:g.20729_20734del
LRG_1344p1:p.Ile458_Asn459del
NC_000005.9:g.137895587_137895592del
NM_004134.6:c.1373_1378del

Links:

OMIM: 600548.0002; dbSNP: rs869312659

NCBI 1000 Genomes Browser:

rs869312659

Molecular consequence:

NM_004134.7:c.1373_1378del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Autosomal dominant sideroblastic anemia
Synonyms:: Anemia, sideroblastic, 4
Identifiers:: MONDO: MONDO:0008422; MedGen: C4225428; Orphanet: 260305; OMIM: 182170

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000265505	OMIM	no assertion criteria provided	Pathogenic (Jul 12, 2017)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000265505

OMIM

no assertion criteria provided

Pathogenic
(Jul 12, 2017)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9.

Schmitz-Abe K, Ciesielski SJ, Schmidt PJ, Campagna DR, Rahimov F, Schilke BA, Cuijpers M, Rieneck K, Lausen B, Linenberger ML, Sendamarai AK, Guo C, Hofmann I, Newburger PE, Matthews D, Shimamura A, Snijders PJ, Towne MC, Niemeyer CM, Watson HG, Dziegiel MH, Heeney MM, et al.

Blood. 2015 Dec 17;126(25):2734-8. doi: 10.1182/blood-2015-09-659854. Epub 2015 Oct 21.

PubMed [citation]

PMID:: 26491070
PMCID:: PMC4683334

Details of each submission

From OMIM, SCV000265505.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a father, daughter, and son with sideroblastic anemia mapping to chromosome 5q (SIDBA4; 182170), Schmitz-Abe et al. (2015) identified heterozygosity for a 6-bp deletion (c.1373_1378del, NM_004134.6) in the HSPA9 gene, resulting in an in-frame deletion of 2 amino acids (I458_N459del). All 3 affected individuals also carried the minor T allele of the synonymous SNP rs10117 (c.1933T) in trans. Analysis of individuals homozygous for the T allele showed that they expressed approximately 50% of HSPA9 mRNA and 80% of HSPA9 protein, compared to individuals homozygous for the C allele. However, there was substantial overlap in the level of expression in the homozygous groups, with some C allele homozygotes having as little mRNA or protein expression as the majority of T homozygotes. Schmitz-Abe et al. (2015) suggested that rs10117 T or a linked variant determines expression of the HSPA9 sideroblastic anemia phenotype in patients with a single unambiguously deleterious allele, but that the T allele itself is not deterministic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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