Variant 19-12701448-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001382241.1(TNPO2):c.2592C>T(p.Leu864Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,613,834 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 43 hom. )

Consequence

TNPO2
NM_001382241.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

TNPO2 (HGNC:19998): (transportin 2) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TNPO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-12701448-G-A is Benign according to our data. Variant chr19-12701448-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.52 with no splicing effect.

BS2

High AC in GnomAd4 at 919 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO2	NM_001382241.1 link	c.2592C>T	p.Leu864Leu	synonymous_variant	25/26	ENST00000425528.6	NP_001369170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO2	ENST00000425528.6 link	c.2592C>T	p.Leu864Leu	synonymous_variant	25/26	5	NM_001382241.1	ENSP00000407182.1		O14787-1

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

918

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00613

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00663

AC:

1652

AN:

249166

Hom.:

AF XY:

0.00677

AC XY:

915

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.00516

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.00626

Gnomad OTH exome

AF:

0.00926

GnomAD4 exome

AF:

0.00573

AC:

8377

AN:

1461616

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

4106

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00564

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.00544

Gnomad4 OTH exome

AF:

0.00593

GnomAD4 genome

AF:

0.00604

AC:

919

AN:

152218

Hom.:

Cov.:

AF XY:

0.00688

AC XY:

512

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0279

Gnomad4 NFE

AF:

0.00615

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00576

Hom.:

Bravo

AF:

0.00446

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	TNPO2: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.2

DANN

Benign

0.85

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