Variant chr5-72855931-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000337273.10(TNPO1):c.355+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,612,512 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 6 hom. )

Consequence

TNPO1
ENST00000337273.10 splice_region, intron

Scores

Splicing: ADA: 0.00005385

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0840

Variant links:

Genes affected

TNPO1 (HGNC:6401): (transportin 1) This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in several transcript variants encoding different proteins. [provided by RefSeq, Jun 2018]

TNPO1 links:

TNPO1 (HGNC:):

TNPO1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-72855931-A-G is Benign according to our data. Variant chr5-72855931-A-G is described in ClinVar as [Benign]. Clinvar id is 3035166.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00641 (977/152366) while in subpopulation AFR AF= 0.0225 (937/41584). AF 95% confidence interval is 0.0213. There are 11 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 977 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO1	NM_002270.4 linkuse as main transcript	c.355+8A>G		splice_region_variant, intron_variant		ENST00000337273.10	NP_002261.3	Q92973-1A0A024RAM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO1	ENST00000337273.10 linkuse as main transcript	c.355+8A>G		splice_region_variant, intron_variant		1	NM_002270.4	ENSP00000336712.5		Q92973-1

Frequencies

GnomAD3 genomes

AF:

0.00638

AC:

971

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00161

AC:

402

AN:

249422

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.000674

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000824

GnomAD4 exome

AF:

0.000615

AC:

898

AN:

1460146

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

357

AN XY:

726392

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.000945

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00641

AC:

977

AN:

152366

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

466

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.00684

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TNPO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000054

dbscSNV1_RF

Benign

0.0

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