Variant rs539653012 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_012470.4(TNPO3):c.2274-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,611,888 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

TNPO3
NM_012470.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.78

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 -16 ACMG points.

BP6

Variant 7-128972591-GA-G is Benign according to our data. Variant chr7-128972591-GA-G is described in ClinVar as [Benign]. Clinvar id is 284887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00215 (328/152284) while in subpopulation AFR AF= 0.00768 (319/41544). AF 95% confidence interval is 0.00698. There are 1 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 328 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4 linkuse as main transcript	c.2274-10del		splice_polypyrimidine_tract_variant, intron_variant		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.2274-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012470.4	ENSP00000265388	P1	Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000668

AC:

166

AN:

248544

Hom.:

AF XY:

0.000447

AC XY:

AN XY:

134328

show subpopulations

Gnomad AFR exome

AF:

0.00920

Gnomad AMR exome

AF:

0.000470

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000221

AC:

322

AN:

1459604

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

134

AN XY:

726018

show subpopulations

Gnomad4 AFR exome

AF:

0.00803

Gnomad4 AMR exome

AF:

0.000518

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152284

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00768

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00249

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

Eurofins Ntd Llc (ga)

Dec 08, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

- -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 9

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