rs7759854

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_020750.3(XPO5):c.*165G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 1,058,394 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 339 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 212 hom. )

Consequence

XPO5
NM_020750.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.294

Publications

6 publications found

Variant links:

Genes affected

XPO5 (HGNC:17675): (exportin 5) This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

XPO5 links:

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

POLR1C Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 11
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Treacher Collins syndrome 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
Treacher-Collins syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.098).

BP6

Variant 6-43523703-C-T is Benign according to our data. Variant chr6-43523703-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178765.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020750.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XPO5	NM_020750.3	MANE Select	c.*165G>A	3_prime_UTR	Exon 32 of 32	NP_065801.1	Q9HAV4
POLR1C	NM_001318876.2		c.922+2655C>T	intron	N/A	NP_001305805.1	O15160-2
POLR1C	NM_001363658.2		c.922+2655C>T	intron	N/A	NP_001350587.1	A0A2R8YEZ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XPO5	ENST00000265351.12	TSL:1 MANE Select	c.*165G>A	3_prime_UTR	Exon 32 of 32	ENSP00000265351.7	Q9HAV4
POLR1C	ENST00000304004.7	TSL:1	c.922+2655C>T	intron	N/A	ENSP00000307212.3	O15160-2
XPO5	ENST00000943409.1		c.*165G>A	3_prime_UTR	Exon 32 of 32	ENSP00000613468.1

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5448

AN:

152162

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.00891

AC:

2197

AN:

246472

AF XY:

0.00680

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00646

Gnomad ASJ exome

AF:

0.000902

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.00365

GnomAD4 exome

AF:

0.00412

AC:

3731

AN:

906114

Hom.:

212

Cov.:

AF XY:

0.00348

AC XY:

1649

AN XY:

474430

show subpopulations

African (AFR)

AF:

0.125

AC:

2853

AN:

22794

American (AMR)

AF:

0.00711

AC:

313

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.00124

AC:

AN:

22614

East Asian (EAS)

AF:

0.00

AC:

AN:

37124

South Asian (SAS)

AF:

0.000268

AC:

AN:

74530

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52758

Middle Eastern (MID)

AF:

0.00449

AC:

AN:

4678

European-Non Finnish (NFE)

AF:

0.000241

AC:

146

AN:

605602

Other (OTH)

AF:

0.00831

AC:

349

AN:

41984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

167

335

502

670

837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0359

AC:

5461

AN:

152280

Hom.:

339

Cov.:

AF XY:

0.0346

AC XY:

2581

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.125

AC:

5172

AN:

41532

American (AMR)

AF:

0.0122

AC:

187

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68028

Other (OTH)

AF:

0.0280

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

255

510

766

1021

1276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0136

Hom.:

182

Bravo

AF:

0.0404

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.2

(source)

DANN

Benign

0.86

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over