NM_001371596.2(MFSD8):c.1307T>C (p.Met436Thr) AND Neuronal ceroid lipofuscinosis 7

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 13, 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:: RCV001993086.4

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1307T>C (p.Met436Thr)]

NM_001371596.2(MFSD8):c.1307T>C (p.Met436Thr)

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.1307T>C (p.Met436Thr)

HGVS:

NC_000004.12:g.127921567A>G
NG_008657.1:g.49418T>C
NM_001363520.3:c.1106T>C
NM_001363521.3:c.992T>C
NM_001371590.2:c.1172T>C
NM_001371591.2:c.1307T>C
NM_001371592.2:c.1313T>C
NM_001371593.2:c.1193T>C
NM_001371594.2:c.1160T>C
NM_001371595.1:c.1025T>C
NM_001371596.2:c.1307T>CMANE SELECT
NM_001410765.1:c.857T>C
NM_001410766.1:c.*192T>C
NM_152778.4:c.1307T>C
NP_001350449.1:p.Met369Thr
NP_001350449.1:p.Met369Thr
NP_001350450.1:p.Met331Thr
NP_001350450.1:p.Met331Thr
NP_001358519.1:p.Met391Thr
NP_001358519.1:p.Met391Thr
NP_001358520.1:p.Met436Thr
NP_001358520.1:p.Met436Thr
NP_001358521.1:p.Met438Thr
NP_001358521.1:p.Met438Thr
NP_001358522.1:p.Met398Thr
NP_001358522.1:p.Met398Thr
NP_001358523.1:p.Met387Thr
NP_001358523.1:p.Met387Thr
NP_001358524.1:p.Met342Thr
NP_001358525.1:p.Met436Thr
NP_001397694.1:p.Met286Thr
NP_689991.1:p.Met436Thr
LRG_833t1:c.1307T>C
LRG_833t2:c.1307T>C
LRG_833:g.49418T>C
LRG_833p1:p.Met436Thr
LRG_833p2:p.Met436Thr
NC_000004.11:g.128842722A>G
NM_001363520.2:c.1106T>C
NM_001363521.2:c.992T>C
NM_001371590.1:c.1172T>C
NM_001371591.1:c.1307T>C
NM_001371592.1:c.1313T>C
NM_001371593.1:c.1193T>C
NM_001371594.1:c.1160T>C

Protein change:

M286T

Links:

dbSNP: rs1405931975

NCBI 1000 Genomes Browser:

rs1405931975

Molecular consequence:

NM_001363520.3:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363521.3:c.992T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371590.2:c.1172T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371591.2:c.1307T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371592.2:c.1313T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371593.2:c.1193T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371594.2:c.1160T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371595.1:c.1025T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371596.2:c.1307T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001410765.1:c.857T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_152778.4:c.1307T>C - 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
SCV002229075	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 13, 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

SCV002229075

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 13, 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, SCV002229075.2

#	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 methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 436 of the MFSD8 protein (p.Met436Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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