1-230979251-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022786.3(ARV1):c.148del(p.His50ThrfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
ARV1
NM_022786.3 frameshift
NM_022786.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.772
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
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-230979251-AC-A is Pathogenic according to our data. Variant chr1-230979251-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 2473859.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARV1 | NM_022786.3 | c.148del | p.His50ThrfsTer4 | frameshift_variant | 1/6 | ENST00000310256.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARV1 | ENST00000310256.7 | c.148del | p.His50ThrfsTer4 | frameshift_variant | 1/6 | 1 | NM_022786.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152108Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome Cov.: 31
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 08, 2023 | The c.148delC (p.H50Tfs*4) alteration, located in exon 1 (coding exon 1) of the ARV1 gene, consists of a deletion of one nucleotide at position 148, causing a translational frameshift with a predicted alternate stop codon after 4 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. - |
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
Publications
No publications associated with this variant yet.