20-57367041-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003610.4(RAE1):​c.496G>T​(p.Val166Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V166I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RAE1
NM_003610.4 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20709449).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAE1NM_003610.4 linkc.496G>T p.Val166Phe missense_variant Exon 7 of 12 ENST00000395841.7 NP_003601.1 P78406

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAE1ENST00000395841.7 linkc.496G>T p.Val166Phe missense_variant Exon 7 of 12 1 NM_003610.4 ENSP00000379182.2 P78406

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251408
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74236
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T;T;.;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
.;.;D;D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.83
L;L;.;L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
0.27
B;B;P;B
Vest4
0.38
MutPred
0.43
Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);
MVP
0.41
MPC
1.3
ClinPred
0.60
D
GERP RS
4.9
Varity_R
0.67
gMVP
0.22

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: rs761437706; hg19: chr20-55942097; API