Variant rs7756 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003292.3(TPR):c.*1407A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 787,338 control chromosomes in the GnomAD database, including 162,257 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 0.63 ( 30693 hom., cov: 32)

Exomes 𝑓: 0.64 ( 131564 hom. )

Consequence

TPR
NM_003292.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.405

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:

PRG4 (HGNC:9364): (proteoglycan 4) The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PRG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPR	NM_003292.3 linkuse as main transcript	c.*1407A>C		3_prime_UTR_variant	51/51	ENST00000367478.9	NP_003283.2
PRG4	NM_005807.6 linkuse as main transcript	c.3991+192T>G		intron_variant		ENST00000445192.7	NP_005798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPR	ENST00000367478.9 linkuse as main transcript	c.*1407A>C		3_prime_UTR_variant	51/51	1	NM_003292.3	ENSP00000356448	P1	P12270-1
PRG4	ENST00000445192.7 linkuse as main transcript	c.3991+192T>G		intron_variant		5	NM_005807.6	ENSP00000399679	P2	Q92954-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96367

AN:

151854

Hom.:

30638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.609

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.602

GnomAD4 exome

AF:

0.641

AC:

407486

AN:

635364

Hom.:

131564

Cov.:

AF XY:

0.637

AC XY:

208806

AN XY:

327770

show subpopulations

Gnomad4 AFR exome

AF:

0.631

Gnomad4 AMR exome

AF:

0.594

Gnomad4 ASJ exome

AF:

0.547

Gnomad4 EAS exome

AF:

0.670

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.656

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.635

AC:

96475

AN:

151974

Hom.:

30693

Cov.:

AF XY:

0.634

AC XY:

47076

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.629

Gnomad4 AMR

AF:

0.609

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.657

Gnomad4 NFE

AF:

0.653

Gnomad4 OTH

AF:

0.605

Alfa

AF:

0.642

Hom.:

53851

Bravo

AF:

0.632

Asia WGS

AF:

0.645

AC:

2240

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.87

DANN

Benign

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over