rs3763600

Variant names:

• chr9-128536311-A-G
• rs3763600
• NM_001003722.2:c.1647-44A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-128536311-A-G
• chr9-128536311-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001003722.2(GLE1):​c.1647-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,573,116 control chromosomes in the GnomAD database, including 45,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6249 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39438 hom.)
• Consequence: GLE1 NM_001003722.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.646
• Publications: 6 publications found

Genes affected

GLE1 (HGNC:4315): (GLE1 RNA export mediator) This gene encodes a predicted 75-kDa polypeptide with high sequence and structure homology to yeast Gle1p, which is nuclear protein with a leucine-rich nuclear export sequence essential for poly(A)+RNA export. Inhibition of human GLE1L by microinjection of antibodies against GLE1L in HeLa cells resulted in inhibition of poly(A)+RNA export. Immunoflourescence studies show that GLE1L is localized at the nuclear pore complexes. This localization suggests that GLE1L may act at a terminal step in the export of mature RNA messages to the cytoplasm. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GLE1 Gene-Disease associations (from GenCC):

• lethal arthrogryposis-anterior horn cell disease syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• lethal congenital contracture syndrome 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

ENSG00000228395 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 9-128536311-A-G is Benign according to our data. Variant chr9-128536311-A-G is described in ClinVar as Benign. ClinVar VariationId is 256858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003722.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLE1	NM_001003722.2	MANE Select	c.1647-44A>G		intron	N/A	NP_001003722.1
	GLE1	NM_001411013.1		c.1674-44A>G		intron	N/A	NP_001397942.1
	GLE1	NM_001499.2		c.1647-44A>G		intron	N/A	NP_001490.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLE1	ENST00000309971.9	TSL:1 MANE Select	c.1647-44A>G		intron	N/A	ENSP00000308622.5
	GLE1	ENST00000372770.4	TSL:1	c.1647-44A>G		intron	N/A	ENSP00000361856.4
	GLE1	ENST00000684463.1		n.241A>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41279 AN: 151968 Hom.: 6239 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.267 AC: 66527 AN: 248878 AF XY: 0.264

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.226 AC: 320503 AN: 1421030 Hom.: 39438 Cov.: 24 AF XY: 0.227 AC XY: 161201 AN XY: 708586

African (AFR) AF: 0.386 AC: 12522 AN: 32446

American (AMR) AF: 0.300 AC: 13231 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4220 AN: 25396

East Asian (EAS) AF: 0.475 AC: 18146 AN: 38186

South Asian (SAS) AF: 0.314 AC: 26770 AN: 85228

European-Finnish (FIN) AF: 0.235 AC: 12223 AN: 51916

Middle Eastern (MID) AF: 0.254 AC: 1422 AN: 5608

European-Non Finnish (NFE) AF: 0.202 AC: 218099 AN: 1079748

Other (OTH) AF: 0.238 AC: 13870 AN: 58382

GnomAD4 genome AF: 0.272 AC: 41320 AN: 152086 Hom.: 6249 Cov.: 32 AF XY: 0.276 AC XY: 20527 AN XY: 74332

African (AFR) AF: 0.376 AC: 15614 AN: 41514

American (AMR) AF: 0.258 AC: 3938 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2407 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2680 AN: 10580

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13726 AN: 67966

Other (OTH) AF: 0.255 AC: 537 AN: 2106

Alfa AF: 0.229 Hom.: 836

Bravo AF: 0.280

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Lethal arthrogryposis-anterior horn cell disease syndrome (1)
-	-	1	Lethal congenital contracture syndrome 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3763600; hg19: chr9-131298590; COSMIC: COSV59408109; COSMIC: COSV59408109;