NM_003610.4:c.288+2479C>T

Variant names:

• chr20-57359017-C-T
• rs1418296529
• NM_003610.4:c.288+2479C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003610.4(RAE1):​c.288+2479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,522,816 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: RAE1 NM_003610.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21541816).
• BS2: High AC in GnomAd4 at 5 AD gene.

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+2479C>T		intron	N/A	NP_003601.1	P78406
	RAE1	NM_001015885.2		c.288+2479C>T		intron	N/A	NP_001015885.1	P78406

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAE1	ENST00000395841.7	TSL:1 MANE Select	c.288+2479C>T		intron	N/A	ENSP00000379182.2	P78406
	RAE1	ENST00000527947.5	TSL:1	c.288+2479C>T		intron	N/A	ENSP00000432609.1	E9PQ57
	RAE1	ENST00000395840.6	TSL:1	c.288+2479C>T		intron	N/A	ENSP00000379181.2	P78406

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000713 AC: 9 AN: 126310 AF XY: 0.0000726

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000968

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 18 AN: 1370474 Hom.: 0 Cov.: 29 AF XY: 0.0000163 AC XY: 11 AN XY: 676198

African (AFR) AF: 0.00 AC: 0 AN: 30594

American (AMR) AF: 0.00 AC: 0 AN: 32468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24528

East Asian (EAS) AF: 0.000516 AC: 18 AN: 34896

South Asian (SAS) AF: 0.00 AC: 0 AN: 75944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071214

Other (OTH) AF: 0.00 AC: 0 AN: 56964

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000962 AC: 5 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	5.2
DANN	Benign	0.82
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.42	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.9
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.40
Vest4		0.33
MVP		0.15
ClinPred		0.23	T
GERP RS		0.42
PromoterAI		0.0091	Neutral
Varity_R		0.77
gMVP		0.011

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1418296529; hg19: chr20-55934073;