NM_001365902.3(NFIX):c.515_518del (p.Ile172fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 15, 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:: RCV003809651.1

Allele description [Variation Report for NM_001365902.3(NFIX):c.515_518del (p.Ile172fs)]

NM_001365902.3(NFIX):c.515_518del (p.Ile172fs)

Gene:

NFIX:nuclear factor I X [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_001365902.3(NFIX):c.515_518del (p.Ile172fs)

HGVS:

NC_000019.10:g.13025508_13025511del
NG_032925.2:g.34739_34742del
NG_140480.1:g.720_723del
NM_001271043.2:c.539_542del
NM_001271044.3:c.491_494del
NM_001365902.3:c.515_518delMANE SELECT
NM_001365982.2:c.515_518del
NM_001365983.2:c.374_377del
NM_001365984.2:c.512_515del
NM_001365985.2:c.512_515del
NM_001378404.1:c.491_494del
NM_001378405.1:c.563_566del
NM_002501.4:c.515_518del
NP_001257972.1:p.Ile180fs
NP_001257973.1:p.Ile164fs
NP_001352831.1:p.Ile172fs
NP_001352911.1:p.Ile172fs
NP_001352912.1:p.Ile125fs
NP_001352913.1:p.Ile171fs
NP_001352914.1:p.Ile171fs
NP_001365333.1:p.Ile164fs
NP_001365334.1:p.Ile188fs
NP_002492.2:p.Ile172fs
NC_000019.9:g.13136319_13136322del
NC_000019.9:g.13136322_13136325del

Protein change:

I125fs

Molecular consequence:

NM_001271043.2:c.539_542del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001271044.3:c.491_494del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365902.3:c.515_518del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365982.2:c.515_518del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365983.2:c.374_377del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365984.2:c.512_515del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365985.2:c.512_515del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378404.1:c.491_494del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378405.1:c.563_566del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002501.4:c.515_518del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Marshall-Smith syndrome (MRSHSS)
Identifiers:: MONDO: MONDO:0011244; MedGen: C0265211; Orphanet: 561; OMIM: 602535

Name:: Malan overgrowth syndrome (MALNS)
Synonyms:: Sotos syndrome 2; MALAN SYNDROME
Identifiers:: MONDO: MONDO:0013885; MedGen: C3553660; Orphanet: 420179; OMIM: 614753

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004596349	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20673863, 20949508, 24924640, 25118028, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004596349

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 15, 2023)

germline

clinical testing

PubMed (5)
[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

Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome.

Malan V, Rajan D, Thomas S, Shaw AC, Louis Dit Picard H, Layet V, Till M, van Haeringen A, Mortier G, Nampoothiri S, Puseljić S, Legeai-Mallet L, Carter NP, Vekemans M, Munnich A, Hennekam RC, Colleaux L, Cormier-Daire V.

Am J Hum Genet. 2010 Aug 13;87(2):189-98. doi: 10.1016/j.ajhg.2010.07.001. Epub 2010 Jul 30.

PubMed [citation]

PMID:: 20673863
PMCID:: PMC2917711

Phenotype and natural history in Marshall-Smith syndrome.

Shaw AC, van Balkom ID, Bauer M, Cole TR, Delrue MA, Van Haeringen A, Holmberg E, Knight SJ, Mortier G, Nampoothiri S, Pušeljić S, Zenker M, Cormier-Daire V, Hennekam RC.

Am J Med Genet A. 2010 Nov;152A(11):2714-26. doi: 10.1002/ajmg.a.33709.

PubMed [citation]

PMID:: 20949508

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004596349.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NFIX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile180Lysfs*38) in the NFIX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NFIX are known to be pathogenic (PMID: 20673863, 20949508, 24924640, 25118028).

#	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: Mar 5, 2024

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