NM_012388.4(BLOC1S6):c.130A>G (p.Ile44Val) AND Hermansky-Pudlak syndrome 9

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001369459.5

Allele description

NM_012388.4(BLOC1S6):c.130A>G (p.Ile44Val)

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.130A>G (p.Ile44Val)

HGVS:

NC_000015.10:g.45592182A>G
NG_028194.2:g.9964A>G
NM_001311255.1:c.145A>G
NM_001311256.1:c.145A>G
NM_012388.4:c.130A>GMANE SELECT
NP_001298184.1:p.Ile49Val
NP_001298185.1:p.Ile49Val
NP_036520.1:p.Ile44Val
LRG_883:g.9964A>G
NC_000015.9:g.45884380A>G
NR_132350.1:n.285A>G
NR_132351.2:n.195A>G
NR_132352.2:n.195A>G
NR_132356.2:n.153A>G
NR_132357.2:n.153A>G

Protein change:

I44V

Links:

dbSNP: rs564232908

NCBI 1000 Genomes Browser:

rs564232908

Molecular consequence:

NM_001311255.1:c.145A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001311256.1:c.145A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_012388.4:c.130A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_132350.1:n.285A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132351.2:n.195A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132352.2:n.195A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132356.2:n.153A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132357.2:n.153A>G - 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

Recent activity

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Mus musculus alpha-2-HS-glycoprotein (Ahsg), transcript variant 2, mRNA
Mus musculus alpha-2-HS-glycoprotein (Ahsg), transcript variant 2, mRNA
gi|2443971914|ref|NM_001276449.2|

Nucleotide
Trachypithecus vetulus chromosome 17 marker chr17-4 genomic sequence
Trachypithecus vetulus chromosome 17 marker chr17-4 genomic sequence
gi|386270103|gb|JN103861.1|

Nucleotide
WWOX WW domain containing oxidoreductase [Homo sapiens]
WWOX WW domain containing oxidoreductase [Homo sapiens]
Gene ID:51741

Gene
Gene Links for GEO Profiles (Select 65666145) (1)
Gene
Homologene neighbors for GEO Profiles (Select 65651370) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001565900	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001565900

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

germline

clinical testing

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

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Details of each submission

From Invitae, SCV001565900.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces isoleucine with valine at codon 44 of the BLOC1S6 protein (p.Ile44Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs564232908, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with BLOC1S6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 11, 2024

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