NM_005850.5(SF3B4):c.1060dup (p.Arg354fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 3, 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:: RCV003556235.2

Allele description [Variation Report for NM_005850.5(SF3B4):c.1060dup (p.Arg354fs)]

NM_005850.5(SF3B4):c.1060dup (p.Arg354fs)

Gene:

SF3B4:splicing factor 3b subunit 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_005850.5(SF3B4):c.1060dup (p.Arg354fs)

HGVS:

NC_000001.11:g.149923874dup
NG_032777.1:g.9385dup
NM_005850.5:c.1060dupMANE SELECT
NP_005841.1:p.Arg354fs
NC_000001.10:g.149895759_149895760insG
NC_000001.10:g.149895766dup
NC_000001.11:g.149923867_149923868insG
NM_005850.4:c.1060dupC

Protein change:

R354fs

Links:

dbSNP: rs782357237

NCBI 1000 Genomes Browser:

rs782357237

Molecular consequence:

NM_005850.5:c.1060dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004291992	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22541558, 24003905, 27622494, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004291992

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 3, 2023)

germline

clinical testing

PubMed (4)
[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

Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome.

Bernier FP, Caluseriu O, Ng S, Schwartzentruber J, Buckingham KJ, Innes AM, Jabs EW, Innis JW, Schuette JL, Gorski JL, Byers PH, Andelfinger G, Siu V, Lauzon J, Fernandez BA, McMillin M, Scott RH, Racher H; FORGE Canada Consortium, Majewski J, Nickerson DA, Shendure J, et al.

Am J Hum Genet. 2012 May 4;90(5):925-33. doi: 10.1016/j.ajhg.2012.04.004. Epub 2012 Apr 26.

PubMed [citation]

PMID:: 22541558
PMCID:: PMC3376638

Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause.

Petit F, Escande F, Jourdain AS, Porchet N, Amiel J, Doray B, Delrue MA, Flori E, Kim CA, Marlin S, Robertson SP, Manouvrier-Hanu S, Holder-Espinasse M.

Clin Genet. 2014 Sep;86(3):246-51. doi: 10.1111/cge.12259. Epub 2013 Sep 12.

PubMed [citation]

PMID:: 24003905

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004291992.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 208831). This frameshift has been observed in individual(s) with Nager syndrome (PMID: 22541558, 24003905, 27622494). In at least one individual the variant was observed to be de novo. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change results in a frameshift in the SF3B4 gene (p.Arg354Profs*132). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 71 amino acid(s) of the SF3B4 protein and extend the protein by 60 additional amino acid residues.

#	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: Jan 13, 2025

ClinVar

Relating variation to medicine