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NM_014698.3(TMEM63A):c.1699G>A (p.Gly567Ser) AND Leukodystrophy, hypomyelinating, 19, transient infantile

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 9, 2019
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:
RCV000884698.1

Allele description [Variation Report for NM_014698.3(TMEM63A):c.1699G>A (p.Gly567Ser)]

NM_014698.3(TMEM63A):c.1699G>A (p.Gly567Ser)

Gene:
TMEM63A:transmembrane protein 63A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q42.12
Genomic location:
Preferred name:
NM_014698.3(TMEM63A):c.1699G>A (p.Gly567Ser)
HGVS:
  • NC_000001.11:g.225853727C>T
  • NM_014698.3:c.1699G>AMANE SELECT
  • NP_055513.2:p.Gly567Ser
  • NC_000001.10:g.226041428C>T
  • NM_014698.2:c.1699G>A
Protein change:
G567S; GLY567SER
Links:
OMIM: 618685.0001; dbSNP: rs1576074651
NCBI 1000 Genomes Browser:
rs1576074651
Molecular consequence:
  • NM_014698.3:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

Name:
Leukodystrophy, hypomyelinating, 19, transient infantile
Identifiers:
MONDO: MONDO:0032871; MedGen: C5231463; OMIM: 618688

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001028094OMIM
no assertion criteria provided
Pathogenic
(Dec 9, 2019) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy.

Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI.

Am J Hum Genet. 2019 Nov 7;105(5):996-1004. doi: 10.1016/j.ajhg.2019.09.011. Epub 2019 Oct 3.

PubMed [citation]
PMID:
31587869
PMCID:
PMC6848986

Details of each submission

From OMIM, SCV001028094.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 unrelated men (patients 1 and 2) of European descent with transient infantile hypomyelinating leukodystrophy-19 (HLD19; 618688), Yan et al. (2019) identified a heterozygous c.1699G-A transition (c.1699G-A, NM_014698.2) in the TMEM63A gene, resulting in a gly567-to-ser (G567S) substitution at a conserved residue in the pore-lining domain of transmembrane helix 6. The mutation, which was found by whole-genome sequencing, occurred de novo in patient 1 and was inherited from a deceased father whose medical records were not available in patient 2. Two children of an unaffected sib of patient 2 had transient infantile nystagmus that was not further investigated. The variant was not present in the 1000 Genomes Project or gnomAD databases. Expression of the mutation into HEK293T cells resulted in impaired stretch-activated TMEM63A currents compared to control, suggesting a loss-of-function effect.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 2, 2023