NM_000489.6(ATRX):c.109C>T (p.Arg37Ter) AND X-linked intellectual disability-hypotonic face syndrome

Clinical significance:Pathogenic (Last evaluated: Oct 2, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000680146.3

Allele description [Variation Report for NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)]

NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)

Gene:
ATRX:ATRX chromatin remodeler [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq21.1
Genomic location:
Preferred name:
NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)
HGVS:
  • NC_000023.11:g.77717155G>A
  • NG_008838.3:g.74115C>T
  • NM_000489.6:c.109C>TMANE SELECT
  • NM_138270.5:c.109C>T
  • NP_000480.3:p.Arg37Ter
  • NP_612114.2:p.Arg37Ter
  • LRG_1153:g.74115C>T
  • NC_000023.10:g.76972632G>A
  • NM_000489.3:c.109C>T
  • NM_000489.4:c.109C>T
  • g.76972632G>A
Protein change:
R37*; ARG37TER
Links:
OMIM: 300032.0022; dbSNP: rs122445108
NCBI 1000 Genomes Browser:
rs122445108
Molecular consequence:
  • NM_000489.6:c.109C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_138270.5:c.109C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
X-linked intellectual disability-hypotonic face syndrome
Synonyms:
XLMR-HYPOTONIC FACIES SYNDROME; Mental retardation-hypotonic facies syndrome X-linked, 1; Mental retardation, X-linked, with growth retardation, deafness, and microgenitalism
Identifiers:
MONDO: MONDO:0010663; MedGen: C4759781; Orphanet: 73220; Orphanet: 93970; Orphanet: 93971; Orphanet: 93972; Orphanet: 93973; Orphanet: 93974; Orphanet: 93975; OMIM: 309580

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000807591Baylor Geneticscriteria provided, single submitter
Pathogenic
(Sep 1, 2017)
maternalclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV0020123043billioncriteria provided, single submitter
Pathogenic
(Oct 2, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedmaternalyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A nonsense mutation of the ATRX gene causing mild mental retardation and epilepsy.

Guerrini R, Shanahan JL, Carrozzo R, Bonanni P, Higgs DR, Gibbons RJ.

Ann Neurol. 2000 Jan;47(1):117-21.

PubMed [citation]
PMID:
10632111

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]
PMID:
25326635
PMCID:
PMC4326249
See all PubMed Citations (3)

Details of each submission

From Baylor Genetics, SCV000807591.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing
(GTR000508680.4)
PubMed (3)

Description

This mutation has been previously reported as disease-causing and was found once in our laboratory in an 8-year-old male with intellectual disability, hypotonia, dysmorphic features, GERD, febrile seizure, short stature, mirocephaly.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyesnot providednot providednot provided
(GTR000508680.4)
not providednot providednot providednot provided

From 3billion, SCV002012304.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000011742.7). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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