NM_024598.4(USB1):c.489_492del (p.Asn163fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 16, 2023
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:: RCV001853992.3

Allele description [Variation Report for NM_024598.4(USB1):c.489_492del (p.Asn163fs)]

NM_024598.4(USB1):c.489_492del (p.Asn163fs)

Gene:

USB1:U6 snRNA biogenesis phosphodiesterase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q21

Genomic location:

Preferred name:

NM_024598.4(USB1):c.489_492del (p.Asn163fs)

HGVS:

NC_000016.10:g.58014312_58014315del
NG_027698.1:g.17940_17943del
NM_001195302.2:c.450-3022_450-3019del
NM_001330568.2:c.336_339del
NM_024598.4:c.489_492delMANE SELECT
NP_001317497.1:p.Asn112fs
NP_078874.2:p.Asn163fs
NP_078874.2:p.Asn163fs
LRG_352t1:c.489_492del
LRG_352:g.17940_17943del
LRG_352p1:p.Asn163fs
NC_000016.9:g.58048213_58048216del
NC_000016.9:g.58048216_58048219del
NM_024598.3:c.489_492del

Protein change:

N112fs

Links:

OMIM: 613276.0007; dbSNP: rs777667891

NCBI 1000 Genomes Browser:

rs777667891

Molecular consequence:

NM_001330568.2:c.336_339del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024598.4:c.489_492del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195302.2:c.450-3022_450-3019del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002240652	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21271650, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240652

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 16, 2023)

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

Identification of a novel C16orf57 mutation in Athabaskan patients with Poikiloderma with Neutropenia.

Clericuzio C, Harutyunyan K, Jin W, Erickson RP, Irvine AD, McLean WH, Wen Y, Bagatell R, Griffin TA, Shwayder TA, Plon SE, Wang LL.

Am J Med Genet A. 2011 Feb;155A(2):337-42. doi: 10.1002/ajmg.a.33807. Epub 2010 Dec 22.

PubMed [citation]

PMID:: 21271650
PMCID:: PMC3069503

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, SCV002240652.3

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

Description

This variant is present in population databases (rs777667891, gnomAD 0.004%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the USB1 protein in which other variant(s) (p.Thr167Profs*98) have been determined to be pathogenic (PMID: 21271650). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 496761). This premature translational stop signal has been observed in individual(s) with poikiloderma with neutropenia (PMID: 21271650). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Asn163Lysfs*101) in the USB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 103 amino acid(s) of the USB1 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: Feb 20, 2024

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