NM_001371596.2(MFSD8):c.1316_1322del (p.Thr439fs) AND Neuronal ceroid lipofuscinosis 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 14, 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:: RCV001387412.6

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1316_1322del (p.Thr439fs)]

NM_001371596.2(MFSD8):c.1316_1322del (p.Thr439fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4q28.2

Genomic location:

Preferred name:

NM_001371596.2(MFSD8):c.1316_1322del (p.Thr439fs)

HGVS:

NC_000004.12:g.127921557_127921563del
NG_008657.1:g.49427_49433del
NM_001363520.3:c.1110_1116delCTATACT
NM_001363521.3:c.996_1002delCTATACT
NM_001371590.2:c.1176_1182delCTATACT
NM_001371591.2:c.1311_1317delCTATACT
NM_001371592.2:c.1317_1323delCTATACT
NM_001371593.2:c.1197_1203delCTATACT
NM_001371594.2:c.1164_1170delCTATACT
NM_001371595.1:c.1034_1040del
NM_001371596.2:c.1316_1322delMANE SELECT
NM_001410765.1:c.861_867delCTATACT
NM_001410766.1:c.*196_*202delCTATACT
NM_152778.4:c.1316_1322del
NP_001350449.1:p.Thr372Ilefs
NP_001350449.1:p.Thr372fs
NP_001350450.1:p.Thr334Ilefs
NP_001350450.1:p.Thr334fs
NP_001358519.1:p.Thr394Ilefs
NP_001358519.1:p.Thr394fs
NP_001358520.1:p.Thr439Ilefs
NP_001358520.1:p.Thr439fs
NP_001358521.1:p.Thr441Ilefs
NP_001358521.1:p.Thr441fs
NP_001358522.1:p.Thr401Ilefs
NP_001358522.1:p.Thr401fs
NP_001358523.1:p.Thr390Ilefs
NP_001358523.1:p.Thr390fs
NP_001358524.1:p.Thr345fs
NP_001358525.1:p.Thr439fs
NP_001397694.1:p.Thr289Ilefs
NP_689991.1:p.Thr439fs
LRG_833t1:c.1316_1322del
LRG_833t2:c.1316_1322del
LRG_833:g.49427_49433del
LRG_833p1:p.Thr439fs
LRG_833p2:p.Thr439fs
NC_000004.11:g.128842707_128842713del
NC_000004.11:g.128842712_128842718del
NM_001363520.2:c.1115_1121del
NM_001363521.2:c.1001_1007del
NM_001371590.1:c.1181_1187del
NM_001371591.1:c.1316_1322del
NM_001371592.1:c.1322_1328del
NM_001371593.1:c.1202_1208del
NM_001371594.1:c.1169_1175del

Protein change:

T334fs

Links:

dbSNP: rs2148839459

NCBI 1000 Genomes Browser:

rs2148839459

Molecular consequence:

NM_001363520.3:c.1110_1116delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363521.3:c.996_1002delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371590.2:c.1176_1182delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371591.2:c.1311_1317delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371592.2:c.1317_1323delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371593.2:c.1197_1203delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371594.2:c.1164_1170delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371595.1:c.1034_1040del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371596.2:c.1316_1322del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410765.1:c.861_867delCTATACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152778.4:c.1316_1322del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001588028	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25976102, 28708303, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001588028

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 14, 2022)

germline

clinical testing

PubMed (3)
[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

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

Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients.

Chérot E, Keren B, Dubourg C, Carré W, Fradin M, Lavillaureix A, Afenjar A, Burglen L, Whalen S, Charles P, Marey I, Heide S, Jacquette A, Heron D, Doummar D, Rodriguez D, Billette de Villemeur T, Moutard ML, Guët A, Xavier J, Périsse D, Cohen D, et al.

Clin Genet. 2018 Mar;93(3):567-576. doi: 10.1111/cge.13102. Epub 2017 Oct 4.

PubMed [citation]

PMID:: 28708303

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001588028.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Thr439Ilefs*5) in the MFSD8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acid(s) of the MFSD8 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1074190). This variant disrupts a region of the MFSD8 protein in which other variant(s) (p.Arg482*) have been determined to be pathogenic (PMID: 25976102, 28708303). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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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