rs771715116
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001371279.1(REEP1):c.445C>T(p.Arg149Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,603,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001371279.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP1 | NM_001371279.1 | c.445C>T | p.Arg149Trp | missense_variant | 6/9 | ENST00000538924.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP1 | ENST00000538924.7 | c.445C>T | p.Arg149Trp | missense_variant | 6/9 | 5 | NM_001371279.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240136Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131088
GnomAD4 exome AF: 0.00000482 AC: 7AN: 1451294Hom.: 0 Cov.: 32 AF XY: 0.00000554 AC XY: 4AN XY: 722402
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
Hereditary spastic paraplegia 31 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 149 of the REEP1 protein (p.Arg149Trp). This variant is present in population databases (rs771715116, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with REEP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 577059). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at