NM_032444.4(SLX4):c.3906del (p.Asn1302fs) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 2, 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:: RCV003843586.2

Allele description [Variation Report for NM_032444.4(SLX4):c.3906del (p.Asn1302fs)]

NM_032444.4(SLX4):c.3906del (p.Asn1302fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_032444.4(SLX4):c.3906del (p.Asn1302fs)

HGVS:

NC_000016.10:g.3589732del
NG_028123.1:g.26853del
NG_132877.1:g.336del
NM_032444.4:c.3906delMANE SELECT
NP_115820.2:p.Asn1302Lysfs
NP_115820.2:p.Asn1302fs
LRG_503t1:c.3906del
LRG_503:g.26853del
LRG_503p1:p.Asn1302Lysfs
NC_000016.9:g.3639733del
NM_032444.2:c.3906delC

Protein change:

N1302fs

Molecular consequence:

NM_032444.4:c.3906del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004643684	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 2, 2023)	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

SCV004643684

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 2, 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

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, SCV004643684.1

#	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 has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1302Lysfs*73) 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).

#	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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