Variant rs35060568 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012470.4(TNPO3):c.2154G>T(p.Arg718Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,618 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 53 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.475

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:

TNPO3 (HGNC:):

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=-0.23).

BP6

Variant 7-128975843-C-A is Benign according to our data. Variant chr7-128975843-C-A is described in ClinVar as [Benign]. Clinvar id is 380944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128975843-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.475 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2051/152334) while in subpopulation AFR AF= 0.0464 (1928/41566). AF 95% confidence interval is 0.0447. There are 34 homozygotes in gnomad4. There are 967 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2051 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4 linkuse as main transcript	c.2154G>T	p.Arg718Arg	synonymous_variant	17/23	ENST00000265388.10	NP_036602.1	Q9Y5L0-2A0A024R794B3KMX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.2154G>T	p.Arg718Arg	synonymous_variant	17/23	1	NM_012470.4	ENSP00000265388.5		Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2029

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00367

AC:

922

AN:

251344

Hom.:

AF XY:

0.00290

AC XY:

394

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0480

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00152

AC:

2227

AN:

1461284

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1002

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.0135

AC:

2051

AN:

152334

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

967

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 31, 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

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.9

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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