rs755719552

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003610.4(RAE1):​c.288+2453C>A variant causes a intron change. The variant allele was found at a frequency of 0.000000737 in 1,357,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

RAE1
NM_003610.4 intron

Scores

1
2
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88
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]
MTRNR2L3 (HGNC:37157): (MT-RNR2 like 3 (pseudogene)) Predicted to enable receptor antagonist activity. Predicted to be involved in negative regulation of execution phase of apoptosis. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAE1NM_003610.4 linkc.288+2453C>A intron_variant Intron 4 of 11 ENST00000395841.7 NP_003601.1 P78406

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAE1ENST00000395841.7 linkc.288+2453C>A intron_variant Intron 4 of 11 1 NM_003610.4 ENSP00000379182.2 P78406

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.37e-7
AC:
1
AN:
1357042
Hom.:
0
Cov.:
29
AF XY:
0.00000149
AC XY:
1
AN XY:
669484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000271
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.0040
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
3.6
DANN
Benign
0.67
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.58
D
M_CAP
Benign
0.0011
T
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.96
T
PROVEAN
Pathogenic
-9.0
D
REVEL
Uncertain
0.36
Vest4
0.55
MVP
0.32
ClinPred
0.90
D
GERP RS
0.42
Varity_R
0.48
gMVP
0.051

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-55934047; API