Variant 6-43523597-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_020750.3(XPO5):c.*271A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 659,036 control chromosomes in the GnomAD database, including 1,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.044 ( 184 hom., cov: 32)

Exomes 𝑓: 0.053 ( 875 hom. )

Consequence

XPO5
NM_020750.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0390

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:

POLR1C (HGNC:):

POLR1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 6-43523597-T-C is Benign according to our data. Variant chr6-43523597-T-C is described in ClinVar as [Benign]. Clinvar id is 1227838.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0639 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.*271A>G		3_prime_UTR_variant	32/32	ENST00000265351.12	NP_065801.1	Q9HAV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351 linkuse as main transcript	c.*271A>G		3_prime_UTR_variant	32/32	1	NM_020750.3	ENSP00000265351.7		Q9HAV4

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6629

AN:

152210

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0430

Gnomad ASJ

AF:

0.0384

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0445

Gnomad FIN

AF:

0.0543

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0455

GnomAD4 exome

AF:

0.0529

AC:

26819

AN:

506708

Hom.:

875

Cov.:

AF XY:

0.0528

AC XY:

14680

AN XY:

278282

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.0369

Gnomad4 ASJ exome

AF:

0.0368

Gnomad4 EAS exome

AF:

0.000864

Gnomad4 SAS exome

AF:

0.0394

Gnomad4 FIN exome

AF:

0.0608

Gnomad4 NFE exome

AF:

0.0655

Gnomad4 OTH exome

AF:

0.0497

GnomAD4 genome

AF:

0.0435

AC:

6627

AN:

152328

Hom.:

184

Cov.:

AF XY:

0.0427

AC XY:

3182

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0384

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0445

Gnomad4 FIN

AF:

0.0543

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0598

Hom.:

Bravo

AF:

0.0398

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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