Genetic Variant TPR:c.4912-37G>A (chr1-186335166-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003292.3(TPR):c.4912-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,582,326 control chromosomes in the GnomAD database, including 11,183 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 965 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10218 hom. )

Consequence

TPR
NM_003292.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.958

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder, autosomal recessive 79
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPR	NM_003292.3 link	c.4912-37G>A		intron_variant	Intron 34 of 50	ENST00000367478.9	NP_003283.2	P12270-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPR	ENST00000367478.9 link	c.4912-37G>A		intron_variant	Intron 34 of 50	1	NM_003292.3	ENSP00000356448.3		P12270-1

Frequencies

GnomAD3 genomes

AF:

0.0915

AC:

13897

AN:

151958

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0936

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0958

Gnomad OTH

AF:

0.108

GnomAD2 exomes

AF:

0.119

AC:

27100

AN:

227244

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.0876

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0991

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.106

AC:

151759

AN:

1430250

Hom.:

10218

Cov.:

AF XY:

0.106

AC XY:

75492

AN XY:

710172

show subpopulations

African (AFR)

AF:

0.0259

AC:

818

AN:

31530

American (AMR)

AF:

0.0887

AC:

3350

AN:

37788

Ashkenazi Jewish (ASJ)

AF:

0.0877

AC:

2165

AN:

24686

East Asian (EAS)

AF:

0.404

AC:

15954

AN:

39468

South Asian (SAS)

AF:

0.116

AC:

9526

AN:

81828

European-Finnish (FIN)

AF:

0.110

AC:

5748

AN:

52244

Middle Eastern (MID)

AF:

0.0532

AC:

298

AN:

5598

European-Non Finnish (NFE)

AF:

0.0977

AC:

107236

AN:

1098132

Other (OTH)

AF:

0.113

AC:

6664

AN:

58976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6829

13658

20488

27317

34146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0913

AC:

13890

AN:

152076

Hom.:

965

Cov.:

AF XY:

0.0954

AC XY:

7091

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0303

AC:

1259

AN:

41498

American (AMR)

AF:

0.102

AC:

1556

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0936

AC:

325

AN:

3472

East Asian (EAS)

AF:

0.381

AC:

1969

AN:

5162

South Asian (SAS)

AF:

0.125

AC:

599

AN:

4810

European-Finnish (FIN)

AF:

0.116

AC:

1224

AN:

10584

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0957

AC:

6508

AN:

67980

Other (OTH)

AF:

0.109

AC:

230

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

618

1235

1853

2470

3088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0965

Hom.:

1394

Bravo

AF:

0.0880

Asia WGS

AF:

0.253

AC:

880

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.68

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-186335166-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over