6-43524840-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_020750.3(XPO5):c.3303C>T(p.Tyr1101Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,612,466 control chromosomes in the GnomAD database, including 67,186 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5882 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61304 hom. )

Consequence

XPO5
NM_020750.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.280

Publications

48 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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 -17 ACMG points.

BP6

Variant 6-43524840-G-A is Benign according to our data. Variant chr6-43524840-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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	HGVSp	Effect	Exon Rank	Protein
XPO5	NM_020750.3	MANE Select	c.3303C>T	p.Tyr1101Tyr	synonymous	Exon 30 of 32	NP_065801.1
XPO5	NR_144392.2		n.3615C>T		non_coding_transcript_exon	Exon 31 of 33
POLR1C	NM_001318876.2		c.922+3792G>A		intron	N/A	NP_001305805.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
XPO5	ENST00000265351.12	TSL:1 MANE Select	c.3303C>T	p.Tyr1101Tyr	synonymous	Exon 30 of 32	ENSP00000265351.7
POLR1C	ENST00000304004.7	TSL:1	c.922+3792G>A		intron	N/A	ENSP00000307212.3
XPO5	ENST00000455285.2	TSL:3	c.645C>T	p.Tyr215Tyr	synonymous	Exon 7 of 8	ENSP00000387384.2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40080

AN:

151340

Hom.:

5873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.272

GnomAD2 exomes

AF:

0.300

AC:

74602

AN:

248854

AF XY:

0.297

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.282

AC:

412288

AN:

1461014

Hom.:

61304

Cov.:

AF XY:

0.282

AC XY:

204789

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.167

AC:

5566

AN:

33348

American (AMR)

AF:

0.297

AC:

13290

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7572

AN:

26134

East Asian (EAS)

AF:

0.615

AC:

24404

AN:

39700

South Asian (SAS)

AF:

0.279

AC:

24077

AN:

86232

European-Finnish (FIN)

AF:

0.329

AC:

17579

AN:

53360

Middle Eastern (MID)

AF:

0.221

AC:

1191

AN:

5382

European-Non Finnish (NFE)

AF:

0.271

AC:

301085

AN:

1111834

Other (OTH)

AF:

0.291

AC:

17524

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

18681

37361

56042

74722

93403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10208

20416

30624

40832

51040

<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:

0.265

AC:

40108

AN:

151452

Hom.:

5882

Cov.:

AF XY:

0.269

AC XY:

19939

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.178

AC:

7272

AN:

40890

American (AMR)

AF:

0.278

AC:

4234

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

998

AN:

3470

East Asian (EAS)

AF:

0.622

AC:

3211

AN:

5166

South Asian (SAS)

AF:

0.282

AC:

1361

AN:

4818

European-Finnish (FIN)

AF:

0.328

AC:

3458

AN:

10552

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18618

AN:

67992

Other (OTH)

AF:

0.281

AC:

591

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1482

2964

4445

5927

7409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.268

Hom.:

26021

Bravo

AF:

0.257

Asia WGS

AF:

0.456

AC:

1588

AN:

3478

EpiCase

AF:

0.264

EpiControl

AF:

0.254

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.9

(source)

DANN

Benign

0.74

PhyloP100

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over