NM_032444.4(SLX4):c.1029del (p.Thr345fs) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 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:: RCV003841637.2

Allele description [Variation Report for NM_032444.4(SLX4):c.1029del (p.Thr345fs)]

NM_032444.4(SLX4):c.1029del (p.Thr345fs)

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.1029del (p.Thr345fs)

HGVS:

NC_000016.10:g.3601115del
NG_028123.1:g.15472del
NM_032444.4:c.1029delMANE SELECT
NP_115820.2:p.Thr345Profs
NP_115820.2:p.Thr345fs
LRG_503t1:c.1027del
LRG_503:g.15472del
LRG_503p1:p.Thr345Profs
NC_000016.9:g.3651114del
NC_000016.9:g.3651116del
NM_032444.2:c.1027delT

Protein change:

T345fs

Molecular consequence:

NM_032444.4:c.1029del - 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

Recent activity

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PREDICTED: Mus musculus DEAD box helicase 4 (Ddx4), transcript variant X1, mRNA
PREDICTED: Mus musculus DEAD box helicase 4 (Ddx4), transcript variant X1, mRNA
gi|1907092342|ref|XM_011244618.3|

Nucleotide
NPU ATP-dependent helicase/deoxyribonuclease subunit B [Arabidopsis thaliana]
NPU ATP-dependent helicase/deoxyribonuclease subunit B [Arabidopsis thaliana]
Gene ID:824324

Gene
AT3G51610[sym] AND (alive[prop]) (1)
Gene
PREDICTED: Hibiscus syriacus uncharacterized LOC120197380 (LOC120197380), transc...
PREDICTED: Hibiscus syriacus uncharacterized LOC120197380 (LOC120197380), transcript variant X9, mRNA
gi|1965345846|ref|XM_039198929.1|

Nucleotide
PREDICTED: Hibiscus syriacus uncharacterized LOC120197265 (LOC120197265), mRNA
PREDICTED: Hibiscus syriacus uncharacterized LOC120197265 (LOC120197265), mRNA
gi|1965345644|ref|XM_039198854.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004647538	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 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

SCV004647538

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 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, SCV004647538.1

#	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.Thr345Profs*2) 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

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