VCV000598741.5 - ClinVar

NM_001318852.2(MAPK8IP3):c.111C>G (p.Tyr37Ter)

Germline

Classification

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.

(4)

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.

Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001318852.2(MAPK8IP3):c.111C>G (p.Tyr37Ter)

Variation ID: 598741 Accession: VCV000598741.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.3 16: 1706450 (GRCh38) [ NCBI UCSC ] 16: 1756451 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 16, 2018	Jun 11, 2020	Oct 2, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_001318852.2:c.111C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001305781.1:p.Tyr37Ter	nonsense
NM_001040439.2:c.111C>G	NP_001035529.1:p.Tyr37Ter	nonsense
NM_015133.5:c.111C>G	NP_055948.2:p.Tyr37Ter	nonsense
NC_000016.10:g.1706450C>G
NC_000016.9:g.1756451C>G

... more HGVS ... less HGVS

Protein change

Y37*

Other names

Canonical SPDI

NC_000016.10:1706449:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 605431.0002 dbSNP: rs770703007 VarSome

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
Gene	OMIM	HI score Help 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.
MAPK8IP3		-	-	GRCh38 GRCh37	345	410

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.
MAPK8IP3-related disorder	Likely pathogenic (1)	criteria provided, single submitter	Oct 11, 2018	RCV000735203.2
Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA	Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Oct 2, 2019	RCV000779602.3

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.
Likely pathogenic (Oct 11, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	MAPK8IP3-related disorder (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo	Undiagnosed Diseases Network, NIH Accession: SCV000863409.1 First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018	Number of individuals with the variant: 1 Clinical Features: Nystagmus (present) , Neonatal hypotonia (present) , Hyporeflexia (present) , Hypometric saccades (present) , Global developmental delay (present) , EEG with temporal focal spikes (present) … (more) Nystagmus (present) , Neonatal hypotonia (present) , Hyporeflexia (present) , Hypometric saccades (present) , Global developmental delay (present) , EEG with temporal focal spikes (present) , EEG with parietal focal spikes (present) , Dysarthria (present) (less) Age: 0-9 years Sex: male Ethnicity/Population group: White Tissue: blood
Likely pathogenic (Oct 02, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV001146830.1 First in ClinVar: Jan 20, 2020 Last updated: Jan 20, 2020	Publications: PubMed (1) PubMed: 30612693 Comment: This variant is interpreted as a Likely pathogenic for Neurodevelopmental disorder with or without variable brain abnormalities, autosomal dominant. The following ACMG Tag(s) were applied: … (more) This variant is interpreted as a Likely pathogenic for Neurodevelopmental disorder with or without variable brain abnormalities, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PVS1-Strong. (less)
Likely pathogenic (Feb 07, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA Affected status: yes Allele origin: de novo	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001335363.1 First in ClinVar: Jun 11, 2020 Last updated: Jun 11, 2020	Publications: PubMed (1) PubMed: 30612693 Comment: This variant was identified as de novo (maternity and paternity confirmed).
Pathogenic (May 23, 2019)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER WITH VARIABLE BRAIN ABNORMALITIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV000916280.1 First in ClinVar: May 27, 2019 Last updated: May 27, 2019	Publications: PubMed (1) PubMed: 30612693 Comment on evidence: In a 4-year-old boy (individual 3) with neurodevelopmental disorder with variable brain abnormalities (NEDBA; 618443), Platzer et al. (2019) identified a de novo heterozygous c.111C-G … (more) In a 4-year-old boy (individual 3) with neurodevelopmental disorder with variable brain abnormalities (NEDBA; 618443), Platzer et al. (2019) identified a de novo heterozygous c.111C-G transversion (c.111C-G, NM_015133.4) in the MAPK8IP3 gene, resulting in a tyr37-to-ter (Y37X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Expression of a mutation corresponding to Y37X in C. elegans resulted in an axonal lysosomal density about 88-fold higher than wildtype. The findings were consistent with loss of unc16 (the homologous gene) in C. elegans, which results in impaired axonal transport. Studies of patient cells were not performed. (less)

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

Title	Author	Journal	Year	Link
De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies.	Platzer K	American journal of human genetics	2019	PMID: 30612693

Text-mined citations for rs770703007 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Mar 23, 2024

ClinVar Genomic variation as it relates to human health

NM_001318852.2(MAPK8IP3):c.111C>G (p.Tyr37Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs770703007 ...