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NM_003491.4(NAA10):c.*43A>G AND Microphthalmia, syndromic 1

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jan 14, 2019
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:
RCV001215735.10

Allele description [Variation Report for NM_003491.4(NAA10):c.*43A>G]

NM_003491.4(NAA10):c.*43A>G

Gene:
NAA10:N-alpha-acetyltransferase 10, NatA catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_003491.4(NAA10):c.*43A>G
HGVS:
  • NC_000023.11:g.153929944T>C
  • NG_013220.1:g.1318A>G
  • NG_031987.1:g.10211A>G
  • NM_001256119.2:c.*43A>G
  • NM_001256120.2:c.*43A>G
  • NM_003491.4:c.*43A>GMANE SELECT
  • NC_000023.10:g.153195397T>C
  • NM_003491.3:c.*43A>G
Nucleotide change:
+43A-G, 3-PRIME UTR
Links:
OMIM: 300013.0006; dbSNP: rs1603289772
NCBI 1000 Genomes Browser:
rs1603289772
Molecular consequence:
  • NM_001256119.2:c.*43A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001256120.2:c.*43A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_003491.4:c.*43A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
Functional consequence:
effect on RNA abundance [Variation Ontology: 0010]

Condition(s)

Name:
Microphthalmia, syndromic 1 (MCOPS1)
Synonyms:
ANOP1; Microphthalmia syndromic 4
Identifiers:
MONDO: MONDO:0010671; MedGen: C0796016; Orphanet: 568; Orphanet: 85275; OMIM: 309800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000864214Biesecker Lab/Clinical Genomics Section, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 14, 2019) 		germlineresearch

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

SCV001387496OMIM
no assertion criteria provided
Pathogenic
(Jul 10, 2020) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Graham, C. A., McCleary, B. G., Malcolm, S., Kelly, E. D., Hill, A. J., Johnston, W. P., Nevin, N. C. Linkage analysis in a family with X-linked anophthalmos. (Abstract) J. Med. Genet. 25: 643-only, 1988.

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes61not providednot providednot providedresearch
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

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

X-linked clinical anophthalmos. Localization of the gene to Xq27-Xq28.

Graham CA, Redmond RM, Nevin NC.

Ophthalmic Paediatr Genet. 1991 Mar;12(1):43-8.

PubMed [citation]
PMID:
1679229
See all PubMed Citations (3)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health, SCV000864214.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided6not provided1not provided

From OMIM, SCV001387496.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a 3-generation family from Northern Ireland (family 1) with syndromic microphthalmia (MCOPS1; 309800), originally reported by Graham et al. (1988, 1991), Johnston et al. (2019) identified a c.*43A-G transition (c.*43A-G, NM_003491.3) in the 3-prime UTR of the NAA10 gene (chrX:153,195,397T-C, GRCh37), altering the consensus polyadenylation sequence (PAS) from AATAAA to AATAGA. The mutation, which was not found in the gnomAD database, segregated fully with disease in the family, including in 1 male previously thought to be unaffected, but who exhibited cleft soft palate and an ear tag. One carrier female showed greater than 90% skewing of X inactivation, but the authors noted that females did not show consistent skewing of X inactivation. Analysis by qPCR of patient mRNA showed an approximately 50% decrease in NAA10 mRNA compared to controls, whereas carrier females had similar levels to controls. RNAseq analysis of transcript structure in affected individuals revealed that read depth did not decrease as expected at the PAS in the 3-prime UTR, but declined approximately 600 bp further 3-prime at a predicted second PAS.

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

Last Updated: Nov 24, 2024