rs8043

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012470.4(TNPO3):c.2661C>T(p.Ala887Ala) 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:5

Conservation

PhyloP100: 0.152

Publications

38 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant limb-girdle muscular dystrophy type 1F
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

TNPO3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TNPO3	NM_012470.4 link	c.2661C>T	p.Ala887Ala	synonymous_variant	Exon 21 of 23	ENST00000265388.10	NP_036602.1	Q9Y5L0-2A0A024R794B3KMX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10 link	c.2661C>T	p.Ala887Ala	synonymous_variant	Exon 21 of 23	1	NM_012470.4	ENSP00000265388.5		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

GnomAD2 exomes

AF:

0.471

AC:

118226

AN:

251268

AF XY:

0.475

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 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

African (AFR)

AF:

0.500

AC:

16720

AN:

33436

American (AMR)

AF:

0.315

AC:

14096

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

15566

AN:

26122

East Asian (EAS)

AF:

0.483

AC:

19171

AN:

39652

South Asian (SAS)

AF:

0.460

AC:

39655

AN:

86182

European-Finnish (FIN)

AF:

0.477

AC:

25476

AN:

53396

Middle Eastern (MID)

AF:

0.495

AC:

2849

AN:

5758

European-Non Finnish (NFE)

AF:

0.504

AC:

559948

AN:

1110380

Other (OTH)

AF:

0.497

AC:

29988

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

17675

35350

53024

70699

88374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16274

32548

48822

65096

81370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.488

AC:

74248

AN:

151992

Hom.:

18343

Cov.:

AF XY:

0.484

AC XY:

35943

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.506

AC:

20947

AN:

41432

American (AMR)

AF:

0.386

AC:

5894

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

2101

AN:

3470

East Asian (EAS)

AF:

0.474

AC:

2448

AN:

5168

South Asian (SAS)

AF:

0.463

AC:

2229

AN:

4816

European-Finnish (FIN)

AF:

0.476

AC:

5021

AN:

10544

Middle Eastern (MID)

AF:

0.472

AC:

137

AN:

290

European-Non Finnish (NFE)

AF:

0.498

AC:

33885

AN:

67976

Other (OTH)

AF:

0.495

AC:

1043

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1953

3907

5860

7814

9767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.497

Hom.:

29607

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.2

(source)

DANN

Benign

0.79

PhyloP100

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over