NM_001371596.2(MFSD8):c.1196C>T (p.Thr399Ile) AND Neuronal ceroid lipofuscinosis 7

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 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:: RCV003121563.4

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1196C>T (p.Thr399Ile)]

NM_001371596.2(MFSD8):c.1196C>T (p.Thr399Ile)

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.1196C>T (p.Thr399Ile)

HGVS:

NC_000004.12:g.127921678G>A
NG_008657.1:g.49307C>T
NM_001363520.3:c.995C>T
NM_001363521.3:c.881C>T
NM_001371590.2:c.1061C>T
NM_001371591.2:c.1196C>T
NM_001371592.2:c.1202C>T
NM_001371593.2:c.1082C>T
NM_001371594.2:c.1049C>T
NM_001371595.1:c.914C>T
NM_001371596.2:c.1196C>TMANE SELECT
NM_001410765.1:c.746C>T
NM_001410766.1:c.*81C>T
NM_152778.4:c.1196C>T
NP_001350449.1:p.Thr332Ile
NP_001350449.1:p.Thr332Ile
NP_001350450.1:p.Thr294Ile
NP_001350450.1:p.Thr294Ile
NP_001358519.1:p.Thr354Ile
NP_001358519.1:p.Thr354Ile
NP_001358520.1:p.Thr399Ile
NP_001358520.1:p.Thr399Ile
NP_001358521.1:p.Thr401Ile
NP_001358521.1:p.Thr401Ile
NP_001358522.1:p.Thr361Ile
NP_001358522.1:p.Thr361Ile
NP_001358523.1:p.Thr350Ile
NP_001358523.1:p.Thr350Ile
NP_001358524.1:p.Thr305Ile
NP_001358525.1:p.Thr399Ile
NP_001397694.1:p.Thr249Ile
NP_689991.1:p.Thr399Ile
LRG_833t1:c.1196C>T
LRG_833t2:c.1196C>T
LRG_833:g.49307C>T
LRG_833p1:p.Thr399Ile
LRG_833p2:p.Thr399Ile
NC_000004.11:g.128842833G>A
NM_001363520.2:c.995C>T
NM_001363521.2:c.881C>T
NM_001371590.1:c.1061C>T
NM_001371591.1:c.1196C>T
NM_001371592.1:c.1202C>T
NM_001371593.1:c.1082C>T
NM_001371594.1:c.1049C>T

Protein change:

T249I

Molecular consequence:

NM_001363520.3:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363521.3:c.881C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371590.2:c.1061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371591.2:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371592.2:c.1202C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371593.2:c.1082C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371594.2:c.1049C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371595.1:c.914C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371596.2:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001410765.1:c.746C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_152778.4:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003787539	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003787539

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV003787539.2

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 399 of the MFSD8 protein (p.Thr399Ile). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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