Variant rs11538884 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012470.4(TNPO3):c.2358G>A(p.Leu786=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,613,690 control chromosomes in the GnomAD database, including 2,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 206 hom., cov: 31)

Exomes 𝑓: 0.048 ( 2036 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.569

Variant links:

Genes affected

TNPO3 (HGNC:17103): (transportin 3) The protein encoded by this gene is a nuclear import receptor for serine/arginine-rich (SR) proteins such as the splicing factors SFRS1 and SFRS2. The encoded protein has also been shown to be involved in HIV-1 infection, apparently through interaction with the HIV-1 capsid protein. Several protein-coding and non-coding transcript variants have been found for this gene. [provided by RefSeq, Apr 2020]

TNPO3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 7-128972498-C-T is Benign according to our data. Variant chr7-128972498-C-T is described in ClinVar as [Benign]. Clinvar id is 260264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128972498-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.569 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO3	NM_012470.4 linkuse as main transcript	c.2358G>A	p.Leu786=	synonymous_variant	19/23	ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.2358G>A	p.Leu786=	synonymous_variant	19/23	1	NM_012470.4	P1	Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6734

AN:

151842

Hom.:

205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.0829

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0413

GnomAD3 exomes

AF:

0.0521

AC:

13101

AN:

251272

Hom.:

432

AF XY:

0.0544

AC XY:

7390

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.0342

Gnomad EAS exome

AF:

0.0808

Gnomad SAS exome

AF:

0.0742

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0488

GnomAD4 exome

AF:

0.0481

AC:

70285

AN:

1461730

Hom.:

2036

Cov.:

AF XY:

0.0490

AC XY:

35606

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0337

Gnomad4 EAS exome

AF:

0.0785

Gnomad4 SAS exome

AF:

0.0759

Gnomad4 FIN exome

AF:

0.0990

Gnomad4 NFE exome

AF:

0.0448

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0443

AC:

6732

AN:

151960

Hom.:

206

Cov.:

AF XY:

0.0478

AC XY:

3549

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.0340

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.0827

Gnomad4 SAS

AF:

0.0720

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.0479

Gnomad4 OTH

AF:

0.0408

Alfa

AF:

0.0430

Hom.:

Bravo

AF:

0.0360

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

EpiCase

AF:

0.0505

EpiControl

AF:

0.0481

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.7

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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