Variant 7-129001172-G-C 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.759C>G(p.Leu253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,613,508 control chromosomes in the GnomAD database, including 157,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11264 hom., cov: 31)

Exomes 𝑓: 0.44 ( 146369 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0460

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=-0.45).

BP6

Variant 7-129001172-G-C is Benign according to our data. Variant chr7-129001172-G-C is described in ClinVar as [Benign]. Clinvar id is 260268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-129001172-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.046 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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.759C>G	p.Leu253=	synonymous_variant	6/23	ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.759C>G	p.Leu253=	synonymous_variant	6/23	1	NM_012470.4	P1	Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55022

AN:

151766

Hom.:

11266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.408

AC:

102549

AN:

251434

Hom.:

22233

AF XY:

0.417

AC XY:

56678

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.432

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.443

AC:

647149

AN:

1461622

Hom.:

146369

Cov.:

AF XY:

0.444

AC XY:

322988

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.432

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.362

AC:

55033

AN:

151886

Hom.:

11264

Cov.:

AF XY:

0.362

AC XY:

26883

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.432

Hom.:

4863

Bravo

AF:

0.349

Asia WGS

AF:

0.391

AC:

1361

AN:

3478

EpiCase

AF:

0.457

EpiControl

AF:

0.465

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	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. -

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.1

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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