ClinVar Genomic variation as it relates to human health
NM_057175.5(NAA15):c.239_240del (p.His80fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_057175.5(NAA15):c.239_240del (p.His80fs)
Variation ID: 559844 Accession: VCV000559844.24
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 4q31.1 4: 139336947-139336948 (GRCh38) [ NCBI UCSC ] 4: 140258101-140258102 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 25, 2018 Nov 25, 2023 Oct 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_057175.5:c.239_240del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_476516.1:p.His80fs frameshift NM_057175.5:c.239_240delAT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_057175.3:c.239_240delAT NM_057175.4:c.239_240del NC_000004.12:g.139336947_139336948del NC_000004.11:g.140258101_140258102del NG_053037.1:g.40481_40482del - Protein change
- H80fs
- Other names
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- Canonical SPDI
- NC_000004.12:139336946:AT:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NAA15 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
378 | 422 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Oct 24, 2023 | RCV001008136.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 29, 2017 | RCV001266473.2 | |
See cases
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Pathogenic (1) |
criteria provided, single submitter
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Apr 26, 2021 | RCV001420262.2 |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV000677626.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 16, 2022 | RCV002463726.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001167895.4
First in ClinVar: Mar 16, 2020 Last updated: Nov 25, 2023 |
Comment:
Identified as an apparently de novo variant in a patient with diaphragmatic hernia in the published literature, but detailed clinical information was not provided (PMID: … (more)
Identified as an apparently de novo variant in a patient with diaphragmatic hernia in the published literature, but detailed clinical information was not provided (PMID: 28303347); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28191889, 29656860, 28303347, 34210367) (less)
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Likely pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446417.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Holoprosencephaly sequence (present) , Cleft palate (present)
Sex: female
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Pathogenic
(Jul 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 50
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV001528440.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. A portion of the reported individuals presented cardiovascular defects [PMID 28303347]
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Pathogenic
(Apr 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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See cases
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli
Accession: SCV001622682.1
First in ClinVar: May 23, 2021 Last updated: May 23, 2021 |
Comment:
PVS1_very strong;PP5_strong;PM2_supporting;PM6_moderate
Clinical Features:
Intellectual disability (present) , Seizure (present) , Hypoglycemic encephalopathy (present) , Hypoplasia of the corpus callosum (present) , Delayed speech and language development (present) , … (more)
Intellectual disability (present) , Seizure (present) , Hypoglycemic encephalopathy (present) , Hypoplasia of the corpus callosum (present) , Delayed speech and language development (present) , Hydronephrosis (present) (less)
Sex: male
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Pathogenic
(Dec 22, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002051532.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 11, 2022 |
Comment:
PVS1, PM6_Strong
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Pathogenic
(Sep 29, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001444648.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Unknown
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Autistic disorder of childhood onset (present) , Muscular hypotonia (present) , Tongue tie (present) , Abnormality of oral frenula (present) … (more)
Global developmental delay (present) , Autistic disorder of childhood onset (present) , Muscular hypotonia (present) , Tongue tie (present) , Abnormality of oral frenula (present) , Brisk reflexes (present) , Unsteady gait (present) , Short stature (present) , Dysharmonic delayed bone age (present) , Myopia (disease) (present) , Astigmatism (present) , Atrial septal defect (present) , Imperforate anus (present) , Plagiocephaly (present) , Prominent forehead (present) , Abnormality of globe location (present) , Abnormality of the nasal bridge (present) , Thick vermilion border (present) , Gingival overgrowth (present) , High palate (present) , Dental crowding (present) (less)
Sex: male
Ethnicity/Population group: Caucasian
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011100.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 50
Affected status: yes
Allele origin:
de novo
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV002559202.1
First in ClinVar: Aug 15, 2022 Last updated: Aug 15, 2022 |
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Pathogenic
(Feb 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Global developmental delay
Affected status: yes
Allele origin:
germline
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Human Genetics Bochum, Ruhr University Bochum
Accession: SCV002758627.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
ACMG criteria used to clasify this variant: PVS1, PM6, PM2_SUP
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Pathogenic
(Mar 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 50
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002779055.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 50
Affected status: yes
Allele origin:
maternal
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Daryl Scott Lab, Baylor College of Medicine
Accession: SCV003915704.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Pathogenic
(Jul 07, 2021)
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no assertion criteria provided
Method: literature only
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INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 50, WITH BEHAVIORAL ABNORMALITIES
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000803755.2
First in ClinVar: Aug 25, 2018 Last updated: Jul 10, 2021 |
Comment on evidence:
In a mother and her 2 sons (family 10) and in 6 additional unrelated patients with autosomal dominant intellectual developmental disorder-50 with behavioral abnormalities (MRD50; … (more)
In a mother and her 2 sons (family 10) and in 6 additional unrelated patients with autosomal dominant intellectual developmental disorder-50 with behavioral abnormalities (MRD50; 617787), Cheng et al. (2018) identified a heterozygous 2-bp deletion (c.239_240delAT, NM_057175.4) in exon 3 of the NAA15 gene, predicted to result in a frameshift and premature termination (His80ArgfsTer17). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was found once in the ExAC database. RT-PCR analysis of patient cells showed reduced mutant mRNA levels, consistent with nonsense-mediated mRNA decay and a loss of function. One of the patients (individual 8) had previously been reported as subject 2 in Stessman et al. (2017). (less)
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Pathogenic
(Apr 05, 2022)
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no assertion criteria provided
Method: clinical testing
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Intellectual disability, autosomal dominant 50
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, University Hospital Schleswig-Holstein
Accession: SCV002583438.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies. | Cheng H | American journal of human genetics | 2018 | PMID: 29656860 |
Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. | Longoni M | Human genetics | 2017 | PMID: 28303347 |
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. | Stessman HA | Nature genetics | 2017 | PMID: 28191889 |
Text-mined citations for rs779009256 ...
HelpRecord last updated Jun 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.