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NM_012388.4(BLOC1S6):c.461G>A (p.Arg154Gln) AND Hermansky-Pudlak syndrome 9

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 31, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001990144.4

Allele description [Variation Report for NM_012388.4(BLOC1S6):c.461G>A (p.Arg154Gln)]

NM_012388.4(BLOC1S6):c.461G>A (p.Arg154Gln)

Gene:
BLOC1S6:biogenesis of lysosomal organelles complex 1 subunit 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_012388.4(BLOC1S6):c.461G>A (p.Arg154Gln)
Other names:
p.Arg154Gln
HGVS:
  • NC_000015.10:g.45606456G>A
  • NG_028194.2:g.24238G>A
  • NM_001311255.1:c.476G>A
  • NM_001311256.1:c.*112G>A
  • NM_012388.2:c.461G>A
  • NM_012388.4:c.461G>AMANE SELECT
  • NP_001298184.1:p.Arg159Gln
  • NP_036520.1:p.Arg154Gln
  • LRG_883:g.24238G>A
  • NC_000015.9:g.45898654G>A
  • NM_012388.3:c.461G>A
  • NR_132350.1:n.790G>A
  • NR_132351.2:n.522G>A
  • NR_132352.2:n.438G>A
  • NR_132353.1:n.640G>A
  • NR_132354.1:n.636G>A
  • NR_132355.2:n.296G>A
  • NR_132356.2:n.484G>A
  • NR_132357.2:n.397G>A
  • NR_132358.1:n.386G>A
  • NR_132359.2:n.254G>A
Protein change:
R154Q
Links:
dbSNP: rs145937442
NCBI 1000 Genomes Browser:
rs145937442
Molecular consequence:
  • NM_001311256.1:c.*112G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001311255.1:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012388.4:c.461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_132350.1:n.790G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132351.2:n.522G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132352.2:n.438G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132353.1:n.640G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132354.1:n.636G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132355.2:n.296G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132356.2:n.484G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132357.2:n.397G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132358.1:n.386G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_132359.2:n.254G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hermansky-Pudlak syndrome 9 (HPS9)
Identifiers:
MONDO: MONDO:0013606; MedGen: C3280026; Orphanet: 280663; Orphanet: 79430; OMIM: 614171

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002233801Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 31, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003920459Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 30, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002233801.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 154 of the BLOC1S6 protein (p.Arg154Gln). This variant is present in population databases (rs145937442, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with BLOC1S6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1450432). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920459.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

BLOC1S6 NM_012388.3 exon 5 p.Arg154Gln (c.461G>A): This variant has not been reported in the literature but is present in 0.1% (25/24966) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-45898654-G-A?dataset=gnomad_r2_1). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024