NM_000181.4(GUSB):c.1880G>A (p.Trp627Ter) AND Mucopolysaccharidosis type 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2022
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:: RCV001205414.6

Allele description [Variation Report for NM_000181.4(GUSB):c.1880G>A (p.Trp627Ter)]

NM_000181.4(GUSB):c.1880G>A (p.Trp627Ter)

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.1880G>A (p.Trp627Ter)

HGVS:

NC_000007.14:g.65960973C>T
NG_016197.1:g.26342G>A
NG_051954.1:g.92875C>T
NM_000181.4:c.1880G>AMANE SELECT
NM_001284290.2:c.1442G>A
NM_001293104.2:c.1310G>A
NM_001293105.2:c.1223G>A
NP_000172.2:p.Trp627Ter
NP_001271219.1:p.Trp481Ter
NP_001280033.1:p.Trp437Ter
NP_001280034.1:p.Trp408Ter
NC_000007.13:g.65425960C>T
NM_000181.3:c.1880G>A
NR_120531.2:n.1825G>A

Protein change:

W408*

Links:

dbSNP: rs1236992554

NCBI 1000 Genomes Browser:

rs1236992554

Molecular consequence:

NR_120531.2:n.1825G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000181.4:c.1880G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001284290.2:c.1442G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293104.2:c.1310G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293105.2:c.1223G>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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Homo sapiens ALF transcription elongation factor 4 (AFF4), mRNA
Homo sapiens ALF transcription elongation factor 4 (AFF4), mRNA
gi|1519241714|ref|NM_014423.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001376668	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7680524, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001376668

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 31, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Mutational analysis of a patient with mucopolysaccharidosis type VII, and identification of pseudogenes.

Shipley JM, Klinkenberg M, Wu BM, Bachinsky DR, Grubb JH, Sly WS.

Am J Hum Genet. 1993 Mar;52(3):517-26.

PubMed [citation]

PMID:: 7680524
PMCID:: PMC1682147

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001376668.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GUSB protein in which other variant(s) (p.Trp627Cys) have been determined to be pathogenic (PMID: 7680524). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 936585). This variant has not been reported in the literature in individuals affected with GUSB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp627*) in the GUSB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the GUSB protein.

#	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: Sep 29, 2024

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