Variant 16-3658192-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016292.3(TRAP1):c.2052C>T(p.Asp684=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,613,652 control chromosomes in the GnomAD database, including 3,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 839 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2603 hom. )

Consequence

TRAP1
NM_016292.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

TRAP1 (HGNC:16264): (TNF receptor associated protein 1) This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAP1 links:

DNASE1 (HGNC:2956): (deoxyribonuclease 1) This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

DNASE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 16-3658192-G-A is Benign according to our data. Variant chr16-3658192-G-A is described in ClinVar as [Benign]. Clinvar id is 559145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAP1	NM_016292.3 linkuse as main transcript	c.2052C>T	p.Asp684=	synonymous_variant	18/18	ENST00000246957.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAP1	ENST00000246957.10 linkuse as main transcript	c.2052C>T	p.Asp684=	synonymous_variant	18/18	1	NM_016292.3	P1	Q12931-1

Frequencies

GnomAD3 genomes

AF:

0.0854

AC:

12982

AN:

151932

Hom.:

838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0422

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.0363

Gnomad SAS

AF:

0.0991

Gnomad FIN

AF:

0.0661

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0425

Gnomad OTH

AF:

0.0753

GnomAD3 exomes

AF:

0.0571

AC:

14345

AN:

251366

Hom.:

643

AF XY:

0.0570

AC XY:

7749

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0349

Gnomad EAS exome

AF:

0.0398

Gnomad SAS exome

AF:

0.0987

Gnomad FIN exome

AF:

0.0671

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0504

AC:

73606

AN:

1461602

Hom.:

2603

Cov.:

AF XY:

0.0511

AC XY:

37147

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0268

Gnomad4 ASJ exome

AF:

0.0350

Gnomad4 EAS exome

AF:

0.0455

Gnomad4 SAS exome

AF:

0.0965

Gnomad4 FIN exome

AF:

0.0640

Gnomad4 NFE exome

AF:

0.0430

Gnomad4 OTH exome

AF:

0.0564

GnomAD4 genome

AF:

0.0855

AC:

12994

AN:

152050

Hom.:

839

Cov.:

AF XY:

0.0853

AC XY:

6338

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0421

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.0366

Gnomad4 SAS

AF:

0.0986

Gnomad4 FIN

AF:

0.0661

Gnomad4 NFE

AF:

0.0425

Gnomad4 OTH

AF:

0.0745

Alfa

AF:

0.0480

Hom.:

384

Bravo

AF:

0.0871

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.0429

EpiControl

AF:

0.0382

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 26, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

DANN

Benign

0.52

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

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