rs1039369434
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001371279.1(REEP1):āc.542A>Cā(p.Lys181Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
REEP1
NM_001371279.1 missense
NM_001371279.1 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 3.72
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3541036).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP1 | NM_001371279.1 | c.542A>C | p.Lys181Thr | missense_variant | 6/9 | ENST00000538924.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP1 | ENST00000538924.7 | c.542A>C | p.Lys181Thr | missense_variant | 6/9 | 5 | NM_001371279.1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247086Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134206
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460186Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726492
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GnomAD4 genome ? Cov.: 33
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33
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 31 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This variant has not been reported in the literature in individuals affected with REEP1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 534219). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 181 of the REEP1 protein (p.Lys181Thr). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.;.;.;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;N;N
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;T;D
Sift4G
Benign
T;.;.;.;.;T;.
Polyphen
P;.;.;.;.;.;.
Vest4
MutPred
Loss of methylation at K181 (P = 0.0186);.;.;Loss of methylation at K181 (P = 0.0186);.;.;.;
MVP
MPC
1.8
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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