VCV000006378.4 - ClinVar

NM_003664.5(AP3B1):c.1975G>T (p.Glu659Ter)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

This classification is based on the single submission received

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_003664.5(AP3B1):c.1975G>T (p.Glu659Ter)

Variation ID: 6378 Accession: VCV000006378.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q14.1 5: 78116228 (GRCh38) [ NCBI UCSC ] 5: 77412052 (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	Oct 2, 2019	Oct 2, 2019	Feb 1, 2002

HGVS

Nucleotide	Protein	Molecular consequence
NM_003664.5:c.1975G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003655.3:p.Glu659Ter	nonsense
NM_001271769.2:c.1828G>T	NP_001258698.1:p.Glu610Ter	nonsense
NC_000005.10:g.78116228C>A
NC_000005.9:g.77412052C>A
NG_007268.1:g.183477G>T
LRG_170:g.183477G>T

... more HGVS ... less HGVS

Protein change

E659*, E610*

Other names

Canonical SPDI

NC_000005.10:78116227:C: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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

ClinGen: CA340569 OMIM: 603401.0008 dbSNP: rs121908907 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.
AP3B1		-	-	GRCh38 GRCh37	1001	1012

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.
Hermansky-Pudlak syndrome 2	Pathogenic (1)	no assertion criteria provided	Feb 1, 2002	RCV000006750.6

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.
Pathogenic (Feb 01, 2002) C Contributing to aggregate classification	no assertion criteria provided	HERMANSKY-PUDLAK SYNDROME 2	OMIM Accession: SCV000026942.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 02, 2019	Publications: PubMed (1) PubMed: 11809908 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 glu659-to-ter (E659X) mutation in the AP3B1 gene that was found in compound heterozygous state in a patient with Hermansky-Pudlak syndrome-2 (HPS2; … (more) For discussion of the glu659-to-ter (E659X) mutation in the AP3B1 gene that was found in compound heterozygous state in a patient with Hermansky-Pudlak syndrome-2 (HPS2; 608233) by Huizing et al. (2002), see 603401.0007. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.	Huizing M	Pediatric research	2002	PMID: 11809908

Text-mined citations for rs121908907 ...

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 Apr 13, 2026