Variant 7-129017941-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012470.4(TNPO3):c.321+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,613,082 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 83 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1073 hom. )

Consequence

TNPO3
NM_012470.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.185

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 7-129017941-G-A is Benign according to our data. Variant chr7-129017941-G-A is described in ClinVar as [Benign]. Clinvar id is 260266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-129017941-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0571 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.321+16C>T		intron_variant		ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10 linkuse as main transcript	c.321+16C>T		intron_variant		1	NM_012470.4	P1	Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

3999

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.0326

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0306

AC:

7666

AN:

250750

Hom.:

168

AF XY:

0.0334

AC XY:

4534

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.0491

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0499

Gnomad FIN exome

AF:

0.0293

Gnomad NFE exome

AF:

0.0365

Gnomad OTH exome

AF:

0.0398

GnomAD4 exome

AF:

0.0351

AC:

51347

AN:

1460840

Hom.:

1073

Cov.:

AF XY:

0.0359

AC XY:

26089

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00550

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0465

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0497

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.0369

Gnomad4 OTH exome

AF:

0.0331

GnomAD4 genome

AF:

0.0263

AC:

3997

AN:

152242

Hom.:

Cov.:

AF XY:

0.0262

AC XY:

1951

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00631

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0426

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.0326

Gnomad4 NFE

AF:

0.0369

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0358

Hom.:

103

Bravo

AF:

0.0244

Asia WGS

AF:

0.0220

AC:

AN:

3478

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	GeneDx	Jan 19, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.9

DANN

Benign

0.73

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