20-57366839-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003610.4(RAE1):​c.408C>G​(p.Ile136Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

RAE1
NM_003610.4 missense

Scores

12
7

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.615
Variant links:
Genes affected
RAE1 (HGNC:9828): (ribonucleic acid export 1) Mutations in the Schizosaccharomyces pombe Rae1 and Saccharomyces cerevisiae Gle2 genes have been shown to result in accumulation of poly(A)-containing mRNA in the nucleus, suggesting that the encoded proteins are involved in RNA export. The protein encoded by this gene is a homolog of yeast Rae1. It contains four WD40 motifs, and has been shown to localize to distinct foci in the nucleoplasm, to the nuclear rim, and to meshwork-like structures throughout the cytoplasm. This gene is thought to be involved in nucleocytoplasmic transport, and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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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=0.39677235).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAE1NM_003610.4 linkc.408C>G p.Ile136Met missense_variant Exon 6 of 12 ENST00000395841.7 NP_003601.1 P78406

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAE1ENST00000395841.7 linkc.408C>G p.Ile136Met missense_variant Exon 6 of 12 1 NM_003610.4 ENSP00000379182.2 P78406

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D;D;.;T;T;D
Eigen
Benign
0.022
Eigen_PC
Benign
0.068
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
.;.;D;.;D;D
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.40
T;T;T;T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.5
M;M;.;.;.;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.5
D;D;D;D;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.018
D;D;D;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D;D;D
Polyphen
0.071
B;B;D;.;.;B
Vest4
0.66
MutPred
0.52
Loss of methylation at K137 (P = 0.0226);Loss of methylation at K137 (P = 0.0226);Loss of methylation at K137 (P = 0.0226);Loss of methylation at K137 (P = 0.0226);Loss of methylation at K137 (P = 0.0226);Loss of methylation at K137 (P = 0.0226);
MVP
0.63
MPC
1.8
ClinPred
0.91
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.69
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs386352355; hg19: chr20-55941895; API