NM_032444.4(SLX4):c.1255G>T (p.Glu419Ter) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 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:: RCV002866189.3

Allele description [Variation Report for NM_032444.4(SLX4):c.1255G>T (p.Glu419Ter)]

NM_032444.4(SLX4):c.1255G>T (p.Glu419Ter)

Gene:

SLX4:SLX4 structure-specific endonuclease subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_032444.4(SLX4):c.1255G>T (p.Glu419Ter)

HGVS:

NC_000016.10:g.3597908C>A
NG_028123.1:g.18677G>T
NM_032444.4:c.1255G>TMANE SELECT
NP_115820.2:p.Glu419Ter
NP_115820.2:p.Glu419Ter
LRG_503t1:c.1255G>T
LRG_503:g.18677G>T
LRG_503p1:p.Glu419Ter
NC_000016.9:g.3647909C>A
NM_032444.2:c.1255G>T

Protein change:

E419*

Molecular consequence:

NM_032444.4:c.1255G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

Recent activity

Clear Turn Off Turn On

Bradyrhizobium sp. ARR365 partial glnII gene for glutamine synthetase isoform II...
Bradyrhizobium sp. ARR365 partial glnII gene for glutamine synthetase isoform II, strain ARR365
gi|930190283|emb|LM994333.1|

Nucleotide

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
SCV003226443	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21240277, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003226443

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 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

SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype.

Stoepker C, Hain K, Schuster B, Hilhorst-Hofstee Y, Rooimans MA, Steltenpool J, Oostra AB, Eirich K, Korthof ET, Nieuwint AW, Jaspers NG, Bettecken T, Joenje H, Schindler D, Rouse J, de Winter JP.

Nat Genet. 2011 Feb;43(2):138-41. doi: 10.1038/ng.751. Epub 2011 Jan 16.

PubMed [citation]

PMID:: 21240277

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, SCV003226443.2

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

Description

This sequence change creates a premature translational stop signal (p.Glu419*) in the SLX4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLX4 are known to be pathogenic (PMID: 21240277). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine