1-230990121-ACT-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022786.3(ARV1):c.309_310del(p.Cys104HisfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ARV1
NM_022786.3 frameshift
NM_022786.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.64
Genes affected
ARV1 (HGNC:29561): (ARV1 homolog, fatty acid homeostasis modulator) this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-230990121-ACT-A is Pathogenic according to our data. Variant chr1-230990121-ACT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 996783.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-230990121-ACT-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARV1 | NM_022786.3 | c.309_310del | p.Cys104HisfsTer7 | frameshift_variant | 3/6 | ENST00000310256.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARV1 | ENST00000310256.7 | c.309_310del | p.Cys104HisfsTer7 | frameshift_variant | 3/6 | 1 | NM_022786.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452702Hom.: 0 AF XY: 0.00000554 AC XY: 4AN XY: 722508
GnomAD4 exome
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4
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722508
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Feb 01, 2021 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at