NM_000181.4(GUSB):c.1796C>T (p.Thr599Met) AND Mucopolysaccharidosis type 7

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 14, 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:: RCV001984237.5

Allele description [Variation Report for NM_000181.4(GUSB):c.1796C>T (p.Thr599Met)]

NM_000181.4(GUSB):c.1796C>T (p.Thr599Met)

Gene:

GUSB:glucuronidase beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_000181.4(GUSB):c.1796C>T (p.Thr599Met)

HGVS:

NC_000007.14:g.65961057G>A
NG_016197.1:g.26258C>T
NG_051954.1:g.92959G>A
NM_000181.4:c.1796C>TMANE SELECT
NM_001284290.2:c.1358C>T
NM_001293104.2:c.1226C>T
NM_001293105.2:c.1139C>T
NP_000172.2:p.Thr599Met
NP_001271219.1:p.Thr453Met
NP_001280033.1:p.Thr409Met
NP_001280034.1:p.Thr380Met
NC_000007.13:g.65426044G>A
NM_000181.3:c.1796C>T
NR_120531.2:n.1741C>T

Protein change:

T380M

Links:

dbSNP: rs765983374

NCBI 1000 Genomes Browser:

rs765983374

Molecular consequence:

NM_000181.4:c.1796C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001284290.2:c.1358C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293104.2:c.1226C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293105.2:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_120531.2:n.1741C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 7 (MPS7)
Synonyms:: MPS VII; Mucopolysaccharidosis type VII; MPS 7; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009662; MedGen: C0085132; Orphanet: 584; OMIM: 253220

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RecName: Full=Protein BEX2; AltName: Full=Brain-expressed X-linked protein 2; Sh...
RecName: Full=Protein BEX2; AltName: Full=Brain-expressed X-linked protein 2; Short=hBex2
gi|74752443|sp|Q9BXY8.1|BEX2_HUMAN

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002280208	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002779129	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 16, 2021)	unknown	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

SCV002280208

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 14, 2022)

germline

clinical testing

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

SCV002779129

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 16, 2021)

unknown

clinical testing

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

Help

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
not provided	unknown	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

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 Invitae, SCV002280208.2

#	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 threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 599 of the GUSB protein (p.Thr599Met). This variant is present in population databases (rs765983374, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GUSB-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 methionine 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

From Fulgent Genetics, Fulgent Genetics, SCV002779129.1

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

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

Last Updated: May 1, 2024

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