U.S. flag

An official website of the United States government

NM_001371596.2(MFSD8):c.553G>C (p.Val185Leu) AND Neuronal ceroid lipofuscinosis 7

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 27, 2021
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:
RCV001242649.5

Allele description [Variation Report for NM_001371596.2(MFSD8):c.553G>C (p.Val185Leu)]

NM_001371596.2(MFSD8):c.553G>C (p.Val185Leu)

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.553G>C (p.Val185Leu)
HGVS:
  • NC_000004.12:g.127942045C>G
  • NG_008657.1:g.28940G>C
  • NM_001363520.3:c.553G>C
  • NM_001363521.3:c.439+1707G>C
  • NM_001371590.2:c.418G>C
  • NM_001371591.2:c.553G>C
  • NM_001371592.2:c.553G>C
  • NM_001371593.2:c.439+1707G>C
  • NM_001371594.2:c.553G>C
  • NM_001371595.1:c.418G>C
  • NM_001371596.2:c.553G>CMANE SELECT
  • NM_001410765.1:c.304+1707G>C
  • NM_001410766.1:c.439+1707G>C
  • NM_152778.4:c.553G>C
  • NP_001350449.1:p.Ala185Pro
  • NP_001358519.1:p.Val140Leu
  • NP_001358520.1:p.Val185Leu
  • NP_001358521.1:p.Gly185Arg
  • NP_001358523.1:p.Glu185Gln
  • NP_001358524.1:p.Glu140Gln
  • NP_001358525.1:p.Val185Leu
  • NP_689991.1:p.Val185Leu
  • LRG_833t1:c.553G>C
  • LRG_833t2:c.553G>C
  • LRG_833:g.28940G>C
  • LRG_833p1:p.Val185Leu
  • LRG_833p2:p.Val185Leu
  • NC_000004.11:g.128863200C>G
  • NM_152778.2:c.553G>C
Protein change:
A185P
Links:
dbSNP: rs1740277571
NCBI 1000 Genomes Browser:
rs1740277571
Molecular consequence:
  • NM_001363521.3:c.439+1707G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371593.2:c.439+1707G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001410765.1:c.304+1707G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001410766.1:c.439+1707G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001363520.3:c.553G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371590.2:c.418G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371591.2:c.553G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371592.2:c.553G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371594.2:c.553G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371595.1:c.418G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371596.2:c.553G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152778.4:c.553G>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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001415751Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 27, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001415751.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces valine with leucine at codon 185 of the MFSD8 protein (p.Val185Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC 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. 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. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024