Variant 1-186320378-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_003292.3(TPR):c.6502C>T(p.Pro2168Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,612,620 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 106 hom. )

Consequence

TPR
NM_003292.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.25

Variant links:

Genes affected

TPR (HGNC:12017): (translocated promoter region, nuclear basket protein) This gene encodes a large coiled-coil protein that forms intranuclear filaments attached to the inner surface of nuclear pore complexes (NPCs). The protein directly interacts with several components of the NPC. It is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of this gene with several different kinase genes occur in some neoplasias. [provided by RefSeq, Jul 2008]

TPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, TPR

BP4

Computational evidence support a benign effect (MetaRNN=0.0027826428).

BP6

Variant 1-186320378-G-A is Benign according to our data. Variant chr1-186320378-G-A is described in ClinVar as [Benign]. Clinvar id is 782687.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPR	NM_003292.3 linkuse as main transcript	c.6502C>T	p.Pro2168Ser	missense_variant	46/51	ENST00000367478.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPR	ENST00000367478.9 linkuse as main transcript	c.6502C>T	p.Pro2168Ser	missense_variant	46/51	1	NM_003292.3	P1	P12270-1
TPR	ENST00000467810.1 linkuse as main transcript	n.320C>T		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

790

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00385

GnomAD3 exomes

AF:

0.00890

AC:

2210

AN:

248374

Hom.:

AF XY:

0.00673

AC XY:

907

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.000909

Gnomad AMR exome

AF:

0.0626

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:

0.0000709

Gnomad OTH exome

AF:

0.00728

GnomAD4 exome

AF:

0.00204

AC:

2986

AN:

1460468

Hom.:

106

Cov.:

AF XY:

0.00172

AC XY:

1253

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.0623

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00131

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00518

AC:

788

AN:

152152

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

450

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0470

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.00855

ESP6500AA

AF:

0.000538

AC:

ESP6500EA

AF:

0.000489

AC:

ExAC

AF:

0.00680

AC:

822

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.31

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0069

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.098

Sift4G

Benign

0.47

Polyphen

0.096

Vest4

0.29

MVP

0.27

MPC

1.6

ClinPred

0.050

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.27

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