rs869320621
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP3PP5
The NM_001371279.1(REEP1):c.303+1_303+7delinsAC variant causes a splice donor, splice donor 5th base, intron change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
REEP1
NM_001371279.1 splice_donor, splice_donor_5th_base, intron
NM_001371279.1 splice_donor, splice_donor_5th_base, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.23
Genes affected
REEP1 (HGNC:25786): (receptor accessory protein 1) This gene encodes a mitochondrial protein that functions to enhance the cell surface expression of odorant receptors. Mutations in this gene cause spastic paraplegia autosomal dominant type 31, a neurodegenerative disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 5.3, offset of 38, new splice context is: caaGTgaga. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 2-86254687-ATATTAC-GT is Pathogenic according to our data. Variant chr2-86254687-ATATTAC-GT is described in ClinVar as [Pathogenic]. Clinvar id is 217864.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP1 | NM_001371279.1 | c.303+1_303+7delinsAC | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | ENST00000538924.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP1 | ENST00000538924.7 | c.303+1_303+7delinsAC | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | 5 | NM_001371279.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spinal muscular atrophy, distal, autosomal recessive, 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 17, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at