VCV002505171.2 - ClinVar

NM_001039886.4(ZNF808):c.1448dup (p.Tyr483Ter)

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.

(2)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001039886.4(ZNF808):c.1448dup (p.Tyr483Ter)

Variation ID: 2505171 Accession: VCV002505171.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: 19q13.41 19: 52554363-52554364 (GRCh38) [ NCBI UCSC ] 19: 53057616-53057617 (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	Jun 17, 2023	Oct 26, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001039886.4:c.1448dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001034975.2:p.Tyr483Ter	nonsense
NM_001321424.2:c.1448dup	NP_001308353.1:p.Tyr483Ter	nonsense
NM_001321425.2:c.1448dup	NP_001308354.1:p.Tyr483Ter	nonsense
NM_001321425.2:c.1448dupA		nonsense
NM_001363550.2:c.1241dup	NP_001350479.1:p.Tyr414Ter	nonsense
NC_000019.10:g.52554364dup
NC_000019.9:g.53057617dup

... more HGVS ... less HGVS

Protein change

Y414*, Y483*

Other names

1-BP DUP, 1448A

Canonical SPDI

NC_000019.10:52554363:A:AA

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: 620970.0007 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.
ZNF808		-	-	GRCh38 GRCh37	84	102

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.
See cases	Likely pathogenic (1)	criteria provided, single submitter	-	RCV003233349.1
PANCREATIC AGENESIS 3	Pathogenic (1)	no assertion criteria provided	Oct 23, 2024	RCV004771541.1

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.
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	See cases (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Medical Genetics, Taibah University College of Applied Medical Sciences Accession: SCV003930435.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023	Publications: PubMed (1) PubMed: 37308312 Indication for testing: Neonatal onset diabetes Sex: female
Pathogenic (Oct 23, 2024)	no assertion criteria provided Method: literature only	PANCREATIC AGENESIS 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV005382032.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Publications: PubMed (1) PubMed: 37308312 Comment on evidence: In 3 Saudi sibs with neonatal-onset diabetes mellitus (PAGEN3; 620991), Alqahtani et al. (2023) identified homozygosity for a 1-bp duplication (c.1448dupA, NM_001321425.2) in the last … (more) In 3 Saudi sibs with neonatal-onset diabetes mellitus (PAGEN3; 620991), Alqahtani et al. (2023) identified homozygosity for a 1-bp duplication (c.1448dupA, NM_001321425.2) in the last exon of the ZNF808 gene, causing a frameshift predicted to result in a premature termination codon (Tyr483Ter) within the zinc finger domain. Their consanguineous parents and 3 unaffected sibs were heterozygous for the duplication. The variant was not found in homozygosity in the gnomAD or Saudi Human Genome Program databases. The authors stated that the patients had a normal pancreatic exocrine phenotype, but investigative results were not reported. (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
Biallelic loss of function variant in ZNF808 is associated with non-syndromic neonatal diabetes.	Alqahtani MA	Clinical genetics	2023	PMID: 37308312

Text-mined citations for this variant ...

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_001039886.4(ZNF808):c.1448dup (p.Tyr483Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...