VCV000162753.21 - ClinVar

NM_003664.5(AP3B1):c.1754T>A (p.Val585Glu)

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.

(10)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003664.5(AP3B1):c.1754T>A (p.Val585Glu)

Variation ID: 162753 Accession: VCV000162753.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q14.1 5: 78129204 (GRCh38) [ NCBI UCSC ] 5: 77425028 (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, 2016	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003664.5:c.1754T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003655.3:p.Val585Glu	missense
NM_001271769.2:c.1607T>A	NP_001258698.1:p.Val536Glu	missense
NC_000005.10:g.78129204A>T
NC_000005.9:g.77425028A>T
NG_007268.1:g.170501T>A
LRG_170:g.170501T>A
LRG_170t1:c.1754T>A	LRG_170p1:p.Val585Glu
	O00203:p.Val585Glu

... more HGVS ... less HGVS

Protein change

V585E, V536E

Other names

NM_001271769.1(AP3B1):c.1607T>A(p.Val536Glu)
NM_003664.4(AP3B1):c.1754T>A(p.Val585Glu)

Canonical SPDI

NC_000005.10:78129203:A:T

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.

1000 Genomes Project 30x 0.81730

The Genome Aggregation Database (gnomAD), exomes 0.86110

Exome Aggregation Consortium (ExAC) 0.86283

Trans-Omics for Precision Medicine (TOPMed) 0.90817

The Genome Aggregation Database (gnomAD) 0.91917

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.93280

Links

ClinGen: CA175259 UniProtKB: O00203#VAR_058404 dbSNP: rs6453373 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	800	810

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.
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Nov 12, 2023	RCV000150163.11
Hermansky-Pudlak syndrome	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000324616.5
Hermansky-Pudlak syndrome 2	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001511630.9
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Dec 26, 2018	RCV001682862.3

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.
Benign (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hermansky-Pudlak syndrome 2 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001775253.1 First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021	Sex: mixed
Benign (Dec 26, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001905255.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (Nov 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan Accession: SCV004102615.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Publications: PubMed (1) PubMed: 25741868 Comment: This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary … (more) This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. Only high quality variants are reported. (less) Number of individuals with the variant: 96 Age: <18 years Sex: mixed
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000309768.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Hermansky-Pudlak Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000458298.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Not specified Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803538.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Comment: This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >10% in Exome Aggregation … (more) This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >10% in Exome Aggregation Consortium. (less)
Benign (Feb 21, 2013)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000197056.4 First in ClinVar: Jan 30, 2015 Last updated: Oct 02, 2016	Comment: Val585Glu in exon 16 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 7.6% (655/8600) of … (more) Val585Glu in exon 16 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 7.6% (655/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs6453373). (less) Number of individuals with the variant: 83
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hermansky-Pudlak syndrome 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001718905.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005302268.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
not provided (-)	no classification provided Method: phenotyping only	Not Provided Affected status: unknown Allele origin: unknown	GenomeConnect, ClinGen Accession: SCV002074575.1 First in ClinVar: Feb 11, 2022 Last updated: Feb 11, 2022	Comment: Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more) Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. (less) Clinical Features: Phenotypic abnormality (present) Indication for testing: Diagnostic Age: 40-49 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2020-04-27 Testing laboratory interpretation: Benign

Comment:

Val585Glu in exon 16 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 7.6% (655/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs6453373).

Comment:

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868

Text-mined citations for rs6453373 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_003664.5(AP3B1):c.1754T>A (p.Val585Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs6453373 ...