Genetic Variant RAE1:c.288+2453C>A (chr20-57358991-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88

Publications

0 publications found

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]

RAE1 links:

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]

MTRNR2L3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAE1	NM_003610.4	MANE Select	c.288+2453C>A		intron	N/A	NP_003601.1	P78406
	RAE1	NM_001015885.2		c.288+2453C>A		intron	N/A	NP_001015885.1	P78406

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAE1	ENST00000395841.7	TSL:1 MANE Select	c.288+2453C>A	intron	N/A	ENSP00000379182.2	P78406
RAE1	ENST00000527947.5	TSL:1	c.288+2453C>A	intron	N/A	ENSP00000432609.1	E9PQ57
RAE1	ENST00000395840.6	TSL:1	c.288+2453C>A	intron	N/A	ENSP00000379181.2	P78406

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.37e-7

AC:

AN:

1357042

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

669484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30180

American (AMR)

AF:

0.00

AC:

AN:

31500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24264

East Asian (EAS)

AF:

0.00

AC:

AN:

34160

South Asian (SAS)

AF:

0.00

AC:

AN:

74206

European-Finnish (FIN)

AF:

0.0000271

AC:

AN:

36848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065582

Other (OTH)

AF:

0.00

AC:

AN:

56336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.0040

BayesDel_noAF

Benign

-0.24

CADD

Benign

3.6

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.11

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.58

M_CAP

Benign

0.0011

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.96

PhyloP100

3.9

PROVEAN

Pathogenic

-9.0

REVEL

Uncertain

0.36

Vest4

0.55

MVP

0.32

ClinPred

0.90

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over