Variant rs2293493 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.2205C>T(p.Leu735=) 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

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=-0.37).

BP6

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

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/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4 linkuse as main transcript	c.2205C>T	p.Leu735=	synonymous_variant	18/23	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.2205C>T	p.Leu735=	synonymous_variant	18/23	1	NM_012470.4	ENSP00000265388	P1	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

GnomAD3 exomes

AF:

0.0514

AC:

12937

AN:

251454

Hom.:

433

AF XY:

0.0540

AC XY:

7343

AN XY:

135900

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 SAS exome

AF:

0.0743

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

Gnomad4 AFR exome

AF:

0.00747

Gnomad4 AMR exome

AF:

0.0207

Gnomad4 ASJ exome

AF:

0.0337

Gnomad4 EAS exome

AF:

0.0786

Gnomad4 SAS exome

AF:

0.0760

Gnomad4 FIN exome

AF:

0.0991

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0469

GnomAD4 genome

AF:

0.0415

AC:

6319

AN:

152254

Hom.:

201

Cov.:

AF XY:

0.0455

AC XY:

3387

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00782

Gnomad4 AMR

AF:

0.0328

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.0833

Gnomad4 SAS

AF:

0.0716

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.0479

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0404

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

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.0

DANN

Benign

0.79

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