7-128974936-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012470.4(TNPO3):c.2205C>T(p.Leu735Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,613,834 control chromosomes in the GnomAD database, including 2,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 201 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2032 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.981

Publications

12 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 7-128974936-G-A is Benign according to our data. Variant chr7-128974936-G-A is described in ClinVar as Benign. ClinVar VariationId is 260262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.981 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4 link	c.2205C>T	p.Leu735Leu	synonymous_variant	Exon 18 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.2205C>T	p.Leu735Leu	synonymous_variant	Exon 18 of 23	1	NM_012470.4	ENSP00000265388.5		Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6320

AN:

152136

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00784

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.0835

Gnomad SAS

AF:

0.0709

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0378

GnomAD2 exomes

AF:

0.0514

AC:

12937

AN:

251454

AF XY:

0.0540

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.0809

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0484

GnomAD4 exome

AF:

0.0478

AC:

69838

AN:

1461580

Hom.:

2032

Cov.:

AF XY:

0.0488

AC XY:

35449

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.00747

AC:

250

AN:

33478

American (AMR)

AF:

0.0207

AC:

926

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

882

AN:

26136

East Asian (EAS)

AF:

0.0786

AC:

3118

AN:

39694

South Asian (SAS)

AF:

0.0760

AC:

6550

AN:

86236

European-Finnish (FIN)

AF:

0.0991

AC:

5295

AN:

53414

Middle Eastern (MID)

AF:

0.0531

AC:

306

AN:

5764

European-Non Finnish (NFE)

AF:

0.0447

AC:

49677

AN:

1111752

Other (OTH)

AF:

0.0469

AC:

2834

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

3225

6450

9674

12899

16124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1818

3636

5454

7272

9090

<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:

0.0415

AC:

6319

AN:

152254

Hom.:

201

Cov.:

AF XY:

0.0455

AC XY:

3387

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00782

AC:

325

AN:

41566

American (AMR)

AF:

0.0328

AC:

502

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3472

East Asian (EAS)

AF:

0.0833

AC:

431

AN:

5176

South Asian (SAS)

AF:

0.0716

AC:

345

AN:

4818

European-Finnish (FIN)

AF:

0.113

AC:

1199

AN:

10592

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0479

AC:

3256

AN:

68026

Other (OTH)

AF:

0.0374

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

302

604

907

1209

1511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0402

Hom.:

Bravo

AF:

0.0326

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

EpiCase

AF:

0.0505

EpiControl

AF:

0.0481

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 26, 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. -

PreventionGenetics, part of Exact Sciences

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

- -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.0

(source)

DANN

Benign

0.79

PhyloP100

0.98

Mutation Taster

=100/0

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

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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