NM_001003722.2:c.322-35_322-29delTTTTTTA

Variant names:

• chr9-128515490-CTTATTTT-C
• rs372645952
• NM_001003722.2:c.322-35_322-29delTTTTTTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001003722.2(GLE1):​c.322-35_322-29delTTTTTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,162,682 control chromosomes in the GnomAD database, including 37,221 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6060 hom., cov: 21)
  • Exomes 𝑓: 0.24 (31161 hom.)
• Consequence: GLE1 NM_001003722.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.45
• Publications: 0 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: G2P, Orphanet
• lethal congenital contracture syndrome 1

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

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-128515490-CTTATTTT-C is Benign according to our data. Variant chr9-128515490-CTTATTTT-C is described in ClinVar as Benign. ClinVar VariationId is 256859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLE1	NM_001003722.2	MANE Select	c.322-35_322-29delTTTTTTA		intron	N/A	NP_001003722.1	Q53GS7-1
	GLE1	NM_001411013.1		c.322-35_322-29delTTTTTTA		intron	N/A	NP_001397942.1	A0A804HJ70
	GLE1	NM_001499.2		c.322-35_322-29delTTTTTTA		intron	N/A	NP_001490.1	B3KMG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLE1	ENST00000309971.9	TSL:1 MANE Select	c.322-35_322-29delTTTTTTA		intron	N/A	ENSP00000308622.5	Q53GS7-1
	GLE1	ENST00000372770.4	TSL:1	c.322-35_322-29delTTTTTTA		intron	N/A	ENSP00000361856.4	Q53GS7-2
	GLE1	ENST00000898507.1		c.322-35_322-29delTTTTTTA		intron	N/A	ENSP00000568566.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40783 AN: 151498 Hom.: 6049 Cov.: 21

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.252

GnomAD2 exomes AF: 0.283 AC: 59611 AN: 210280 AF XY: 0.280

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.242 AC: 245122 AN: 1011064 Hom.: 31161 AF XY: 0.244 AC XY: 126919 AN XY: 520328

African (AFR) AF: 0.395 AC: 9692 AN: 24552

American (AMR) AF: 0.307 AC: 12823 AN: 41798

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 3912 AN: 22964

East Asian (EAS) AF: 0.491 AC: 17734 AN: 36108

South Asian (SAS) AF: 0.322 AC: 24087 AN: 74856

European-Finnish (FIN) AF: 0.242 AC: 12128 AN: 50206

Middle Eastern (MID) AF: 0.255 AC: 1263 AN: 4944

European-Non Finnish (NFE) AF: 0.214 AC: 152157 AN: 710138

Other (OTH) AF: 0.249 AC: 11326 AN: 45498

GnomAD4 genome AF: 0.269 AC: 40826 AN: 151618 Hom.: 6060 Cov.: 21 AF XY: 0.274 AC XY: 20265 AN XY: 74070

African (AFR) AF: 0.372 AC: 15326 AN: 41248

American (AMR) AF: 0.255 AC: 3889 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2378 AN: 5136

South Asian (SAS) AF: 0.339 AC: 1628 AN: 4800

European-Finnish (FIN) AF: 0.253 AC: 2660 AN: 10534

Middle Eastern (MID) AF: 0.238 AC: 69 AN: 290

European-Non Finnish (NFE) AF: 0.201 AC: 13650 AN: 67900

Other (OTH) AF: 0.252 AC: 531 AN: 2106

Alfa AF: 0.223 Hom.: 754

Bravo AF: 0.279

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs372645952; hg19: chr9-131277769;