NM_001371596.2(MFSD8):c.1350+1G>A AND Neuronal ceroid lipofuscinosis 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 2, 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:: RCV002611757.3

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1350+1G>A]

NM_001371596.2(MFSD8):c.1350+1G>A

Gene:

MFSD8:major facilitator superfamily domain containing 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q28.2

Genomic location:

Preferred name:

NM_001371596.2(MFSD8):c.1350+1G>A

HGVS:

NC_000004.12:g.127921523C>T
NG_008657.1:g.49462G>A
NM_001363520.3:c.1149+1G>A
NM_001363521.3:c.1035+1G>A
NM_001371590.2:c.1215+1G>A
NM_001371591.2:c.1351G>A
NM_001371592.2:c.1356+1G>A
NM_001371593.2:c.1236+1G>A
NM_001371594.2:c.1203+1G>A
NM_001371595.1:c.1068+1G>A
NM_001371596.2:c.1350+1G>AMANE SELECT
NM_001410765.1:c.900+1G>A
NM_001410766.1:c.*236G>A
NM_152778.4:c.1350+1G>A
NP_001358520.1:p.Val451Ile
LRG_833t1:c.1350+1G>A
LRG_833t2:c.1350+1G>A
LRG_833:g.49462G>A
NC_000004.11:g.128842678C>T

Protein change:

V451I

Molecular consequence:

NM_001410766.1:c.*236G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001371591.2:c.1351G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363520.3:c.1149+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001363521.3:c.1035+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371590.2:c.1215+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371592.2:c.1356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371593.2:c.1236+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371594.2:c.1203+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371595.1:c.1068+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371596.2:c.1350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001410765.1:c.900+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_152778.4:c.1350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis 7 (CLN7)
Synonyms:: MFSD8-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:: MONDO: MONDO:0012588; MedGen: C1838571; Orphanet: 168491; Orphanet: 228366; OMIM: 610951

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003508806	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9177532, 25976102, 28708303, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003508806

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2022)

germline

clinical testing

PubMed (6)
[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

Duodenal obstruction secondary to a metastasis from an adenocarcinoma of the cecum: a case report.

Sebastián JJ, Zaragozano R, Vicente J, Gallego O, Trufero JM.

Am J Gastroenterol. 1997 Jun;92(6):1051-2.

PubMed [citation]

PMID:: 9177532

The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina.

Kohan R, Pesaola F, Guelbert N, Pons P, Oller-Ramírez AM, Rautenberg G, Becerra A, Sims K, Xin W, Cismondi IA, Noher de Halac I.

Biochim Biophys Acta. 2015 Oct;1852(10 Pt B):2301-11. doi: 10.1016/j.bbadis.2015.05.003. Epub 2015 May 11. Review.

PubMed [citation]

PMID:: 25976102

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003508806.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MFSD8 protein in which other variant(s) (p.Arg482*) have been determined to be pathogenic (PMID: 9177532, 25976102, 28708303; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 12 of the MFSD8 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

#	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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