VCV000627544.6 - ClinVar

NM_001379659.1(ZNF142):c.5098C>T (p.Arg1700Trp)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic
Likely pathogenic (1)

1 out of 3 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001379659.1(ZNF142):c.5098C>T (p.Arg1700Trp)

Variation ID: 627544 Accession: VCV000627544.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q35 2: 218640760 (GRCh38) [ NCBI UCSC ] 2: 219505483 (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	May 13, 2019	May 15, 2025	Apr 15, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001379659.1:c.5098C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001366588.1:p.Arg1700Trp	missense
NM_001105537.5:c.4498C>T	NP_001099007.1:p.Arg1500Trp	missense
NM_001366287.3:c.4009C>T	NP_001353216.1:p.Arg1337Trp	missense
NM_001366288.3:c.4009C>T	NP_001353217.1:p.Arg1337Trp	missense
NM_001366289.3:c.4009C>T	NP_001353218.1:p.Arg1337Trp	missense
NM_001366290.3:c.5098C>T	NP_001353219.1:p.Arg1700Trp	missense
NM_001366291.3:c.4498C>T	NP_001353220.1:p.Arg1500Trp	missense
NM_001379660.1:c.5098C>T	NP_001366589.1:p.Arg1700Trp	missense
NM_001379661.1:c.5098C>T	NP_001366590.1:p.Arg1700Trp	missense
NM_001379662.1:c.4498C>T	NP_001366591.1:p.Arg1500Trp	missense
NC_000002.12:g.218640760G>A
NC_000002.11:g.219505483G>A
NG_033099.2:g.23863C>T

... more HGVS ... less HGVS

Protein change

R1500W, R1337W, R1700W

Other names

Canonical SPDI

NC_000002.12:218640759:G:A

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.

The Genome Aggregation Database (gnomAD) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD), exomes 0.00004

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

ClinGen: CA2108604 OMIM: 604083.0006 dbSNP: rs367658234 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.
ZNF142		-	-	GRCh38 GRCh37	461	546

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.
Neurodevelopmental disorder with impaired speech and hyperkinetic movements	Likely pathogenic (3)	criteria provided, single submitter	Apr 15, 2025	RCV000770920.8

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.	Expand all rows Collapse all rows 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 (Apr 15, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Neurodevelopmental disorder with impaired speech and hyperkinetic movements	Tumer Group, Copenhagen University Hospital, Rigshospitalet Accession: SCV006074655.1 First in ClinVar: May 15, 2025 Last updated: May 15, 2025	Observation: 1 Collection method: research Allele origin: unknown Affected status: yes Observation 1 Collection method: research Allele origin: unknown Affected status: yes

Pathogenic (May 10, 2019) N Not contributing to aggregate classification	no assertion criteria provided	NEURODEVELOPMENTAL DISORDER WITH IMPAIRED SPEECH AND HYPERKINETIC MOVEMENTS	OMIM Accession: SCV000902419.1 First in ClinVar: May 13, 2019 Last updated: May 13, 2019	Publications: PubMed (1) PubMed: 31036918 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: For discussion of the c.4498C-T transition (c.4498C-T, NM_001105537.2) in exon 9 of the ZNF142 gene, resulting in an arg1500-to-trp (R1500W) substitution, that was found in … (more) For discussion of the c.4498C-T transition (c.4498C-T, NM_001105537.2) in exon 9 of the ZNF142 gene, resulting in an arg1500-to-trp (R1500W) substitution, that was found in compound heterozygous state in 2 sisters with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM; 618425) by Khan et al. (2019), see 604083.0005. (less)

Uncertain significance (Mar 08, 2019) N Not contributing to aggregate classification	no assertion criteria provided	Neurodevelopmental disorder with impaired speech and hyperkinetic movements (Autosomal recessive inheritance)	Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago Accession: SCV000925594.1 First in ClinVar: Jul 03, 2019 Last updated: Jul 03, 2019 Comment: compound heterozygous	Publications: PubMed (1) PubMed: 31036918 Observation: 1 Collection method: research Allele origin: maternal Affected status: yes more Observation 1 Collection method: research Allele origin: maternal Affected status: yes Number of individuals with the variant: 1 Clinical Features: Intellectual disability (present) , Global developmental delay (present) , Generalized tonic-clonic seizures (present) , Speech apraxia (present) Family history: yes Platform type: whole exome sequencing Testing laboratory: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.	Khan K	Genetics in medicine : official journal of the American College of Medical Genetics	2019	PMID: 31036918

Text-mined citations for rs367658234 ...

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 21, 2026