ClinVar Genomic variation as it relates to human health
NM_001371596.2(MFSD8):c.979del (p.Val327fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001371596.2(MFSD8):c.979del (p.Val327fs)
Variation ID: 2627614 Accession: VCV002627614.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 4q28.2 4: 127930702 (GRCh38) [ NCBI UCSC ] 4: 128851857 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 4, 2023 Nov 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001371596.2:c.979del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001358525.1:p.Val327fs frameshift NM_001363520.3:c.778del NP_001350449.1:p.Val260fs frameshift NM_001363521.3:c.664del NP_001350450.1:p.Val222fs frameshift NM_001371590.2:c.844del NP_001358519.1:p.Val282fs frameshift NM_001371591.2:c.979del NP_001358520.1:p.Val327fs frameshift NM_001371592.2:c.985del NP_001358521.1:p.Val329fs frameshift NM_001371593.2:c.865del NP_001358522.1:p.Val289fs frameshift NM_001371594.2:c.832del NP_001358523.1:p.Val278fs frameshift NM_001371595.1:c.697del NP_001358524.1:p.Val233fs frameshift NM_001410765.1:c.529del NP_001397694.1:p.Val177fs frameshift NM_001410766.1:c.865del NP_001397695.1:p.Val289fs frameshift NM_152778.4:c.979del NP_689991.1:p.Val327fs frameshift NC_000004.12:g.127930702del NC_000004.11:g.128851857del NG_008657.1:g.40283del LRG_833:g.40283del LRG_833t1:c.979del LRG_833p1:p.Val327fs LRG_833t2:c.979del LRG_833p2:p.Val327fs - Protein change
- V177fs, V222fs, V233fs, V260fs, V278fs, V282fs, V289fs, V327fs, V329fs
- Other names
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- Canonical SPDI
- NC_000004.12:127930701:C:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MFSD8 | - | - |
GRCh38 GRCh37 |
942 | 988 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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- | RCV003388904.1 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 7
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Human Genome Lab, NIMHANS, National Institute of Mental Health and Neuro Sciences
Accession: SCV004100680.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
The frameshift deletion NM_152778.4:c.979del has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The NP_689991.1:p.Val327Leufs*87 variant is … (more)
The frameshift deletion NM_152778.4:c.979del has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The NP_689991.1:p.Val327Leufs*87 variant is novel (not in any individuals) in 1000 Genomes, gnomAD as well as in our inhouse database. This variant is predicted to cause loss of normal protein function through protein truncation caused by the frameshift mutation or such an mRNA is predicted to undergo nonsense mediated decay. The frame shifted sequence continues 87 residues until a stop codon is reached. This variant is a frameshift variant which occurs in an exon of MFSD8 upstream of where nonsense mediated decay is predicted to occur. There are 33 downstream pathogenic loss of function variants, with the furthest variant being 155 residues downstream of this variant. This indicates that the region is critical to protein function. The p.Val327Leufs*87 variant is a loss of function variant in the gene MFSD8, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_689991.1:p.E9Dfs*19 and 53 others. In addition, the phenotype of the proband matches with that caused by pathogenic variants in MFSD8 gene. For these reasons, this variant has been classified as Pathogenic (PM2 PVS1 PP4_Strong). (less)
Clinical Features:
Global developmental delay (present) , Developmental regression (present) , Cerebellar ataxia (present) , Optic atrophy (present) , Spasticity (present) , Myoclonus (present) , Abnormality of … (more)
Global developmental delay (present) , Developmental regression (present) , Cerebellar ataxia (present) , Optic atrophy (present) , Spasticity (present) , Myoclonus (present) , Abnormality of extrapyramidal motor function (present) , Cerebral atrophy (present) , Cerebellar atrophy (present) , Curvilinear intracellular accumulation of autofluorescent lipopigment storage material (present) (less)
Age: 0-9 years
Sex: male
Ethnicity/Population group: South Indian Hindu
Geographic origin: South India
Comment on evidence:
This 4-year-old male child, 1st born of consanguineous parentage, with smooth perinatal transition, had premorbid speech delay presented with subacute onset, rapidly progressive, myoclonic epilepsy, … (more)
This 4-year-old male child, 1st born of consanguineous parentage, with smooth perinatal transition, had premorbid speech delay presented with subacute onset, rapidly progressive, myoclonic epilepsy, ataxia, cognitive decline, neuroregression with choreiform movements. On examination, choreiform movements, bilateral hypertonia and exaggerated reflexes were present. MRI Brain showed mild cerebellar atrophy, T2/FLAIR hypointense thalami, T2/FLAIR hyperintensities in the periventricular white matter and diffuse cerebral atrophy. Axillary skin biopsy sent for electron microscopy showed characteristic membrane bound inclusions in the form curvilinear profiles diagnostic of Neuronal ceroid lipofuscinosis. The NP_689991.1:p.Val327Leufs*87 variant in MFSD8 gene was observed in the affected proband in homozygous state, confirming the diagnosis. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Nov 04, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.