Variant chr6-43524840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000265351.12(XPO5):c.3303C>T(p.Tyr1101=) 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. In-silico tool predicts a benign outcome for this variant. 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
ENST00000265351.12 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.280

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 6-43524840-G-A is Benign according to our data. Variant chr6-43524840-G-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO5	NM_020750.3 linkuse as main transcript	c.3303C>T	p.Tyr1101=	synonymous_variant	30/32	ENST00000265351.12	NP_065801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12 linkuse as main transcript	c.3303C>T	p.Tyr1101=	synonymous_variant	30/32	1	NM_020750.3	ENSP00000265351	P1

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

GnomAD3 exomes

AF:

0.300

AC:

74602

AN:

248854

Hom.:

12538

AF XY:

0.297

AC XY:

40112

AN XY:

135022

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 SAS exome

AF:

0.283

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

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.615

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.265

AC:

40108

AN:

151452

Hom.:

5882

Cov.:

AF XY:

0.269

AC XY:

19939

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.269

Hom.:

13239

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.9

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over