rs8043

Variant summary

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

The NM_012470.4(TNPO3):c.2661C>T(p.Ala887=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,611,936 control chromosomes in the GnomAD database, including 199,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18343 hom., cov: 32)

Exomes 𝑓: 0.50 ( 181078 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.152

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-128967330-G-A is Benign according to our data. Variant chr7-128967330-G-A is described in ClinVar as [Benign]. Clinvar id is 260265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128967330-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.152 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 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.2661C>T	p.Ala887=	synonymous_variant	21/23	ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.2661C>T	p.Ala887=	synonymous_variant	21/23	1	NM_012470.4	P1	Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74192

AN:

151874

Hom.:

18327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.471

AC:

118226

AN:

251268

Hom.:

28844

AF XY:

0.475

AC XY:

64510

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.507

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.464

Gnomad FIN exome

AF:

0.475

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.496

AC:

723469

AN:

1459944

Hom.:

181078

Cov.:

AF XY:

0.496

AC XY:

360172

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.596

Gnomad4 EAS exome

AF:

0.483

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.477

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.488

AC:

74248

AN:

151992

Hom.:

18343

Cov.:

AF XY:

0.484

AC XY:

35943

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.605

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.498

Gnomad4 OTH

AF:

0.495

Alfa

AF:

0.500

Hom.:

24093

Bravo

AF:

0.484

Asia WGS

AF:

0.468

AC:

1629

AN:

3478

EpiCase

AF:

0.500

EpiControl

AF:

0.509

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
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

-0.49

Cadd

Benign

6.2

Dann

Benign

0.79

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