NM_001353812.2(ATP11C):c.1244C>A (p.Thr415Asn) AND X-linked congenital hemolytic anemia

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 15, 2018
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:: RCV000678207.2

Allele description [Variation Report for NM_001353812.2(ATP11C):c.1244C>A (p.Thr415Asn)]

NM_001353812.2(ATP11C):c.1244C>A (p.Thr415Asn)

Gene:

ATP11C:ATPase phospholipid transporting 11C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq27.1

Genomic location:

Preferred name:

NM_001353812.2(ATP11C):c.1244C>A (p.Thr415Asn)

Other names:

ATP11C, THR418ASN (1 patient)

HGVS:

NC_000023.11:g.139789451G>T
NG_016550.2:g.148633C>A
NM_001010986.3:c.1253C>A
NM_001353810.2:c.1244C>A
NM_001353811.2:c.1244C>A
NM_001353812.2:c.1244C>AMANE SELECT
NM_173694.5:c.1253C>A
NP_001010986.2:p.Thr418Asn
NP_001340739.2:p.Thr415Asn
NP_001340740.2:p.Thr415Asn
NP_001340741.2:p.Thr415Asn
NP_775965.3:p.Thr418Asn
NC_000023.10:g.138871610G>T
NM_001010986.2:c.1253C>A

Protein change:

T415N; THR418ASN

Links:

OMIM: 300516.0001; dbSNP: rs1556323334

NCBI 1000 Genomes Browser:

rs1556323334

Molecular consequence:

NM_001010986.3:c.1253C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353810.2:c.1244C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353811.2:c.1244C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353812.2:c.1244C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_173694.5:c.1253C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: X-linked congenital hemolytic anemia (HACXL)
Identifiers:: MONDO: MONDO:0060455; MedGen: C4746970; OMIM: 301015

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000804209	OMIM	no assertion criteria provided	Pathogenic (Apr 12, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000883186	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 15, 2018)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 26944472, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000804209

OMIM

no assertion criteria provided

Pathogenic
(Apr 12, 2022)

germline

literature only

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

SCV000883186

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 15, 2018)

germline

curation

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	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia.

Arashiki N, Takakuwa Y, Mohandas N, Hale J, Yoshida K, Ogura H, Utsugisawa T, Ohga S, Miyano S, Ogawa S, Kojima S, Kanno H.

Haematologica. 2016 May;101(5):559-65. doi: 10.3324/haematol.2016.142273. Epub 2016 Mar 4.

PubMed [citation]

PMID:: 26944472
PMCID:: PMC5004368

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 OMIM, SCV000804209.2

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

Description

In a Japanese man with X-linked congenital hemolytic anemia (HACXL; 301015), Arashiki et al. (2016) identified a hemizygous c.1253C-A transversion (c.1253C-A, NM_001010986) in exon 13 of the ATP11C gene, resulting in a thr418-to-asn (T418N) substitution at a conserved residue. The mutation, which was identified by whole-exome sequencing, was found in heterozygous state in the unaffected mother. It was not found in the dbSNP database (builds 132 and 135) or in an in-house database. Flow cytometric analysis showed that the patient's cells had significantly decreased flippase activity (3%) of phosphatidylcholine (PS) at about a 10-fold decrease compared to controls. Similar findings were observed in about half of the mother's erythrocytes, with the other half being similar to wildtype; these findings were consistent with random X inactivation.

#	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

From SIB Swiss Institute of Bioinformatics, SCV000883186.1

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

Description

This variant is interpreted as Likely Pathogenic, for Hemolytic anemia, congenital, X-linked. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/26944472).

#	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: Apr 23, 2022

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