NM_016292.3:c.919C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016292.3(TRAP1):c.919C>G(p.Arg307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,540 control chromosomes in the GnomAD database, including 149,092 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R307H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.36 ( 11462 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137630 hom. )

Consequence

TRAP1
NM_016292.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0150

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

autosomal systemic lupus erythematosus type 16
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

DNASE1 links:

LOC124903630 (HGNC:):

LOC124903630 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 16-3674464-G-C is Benign according to our data. Variant chr16-3674464-G-C is described in ClinVar as Benign. ClinVar VariationId is 260710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAP1	NM_016292.3 link	c.919C>G	p.Arg307Gly	missense_variant	Exon 9 of 18	ENST00000246957.10	NP_057376.2	Q12931-1A0A140VJY2
TRAP1	NM_001272049.2 link	c.760C>G	p.Arg254Gly	missense_variant	Exon 8 of 17		NP_001258978.1	Q12931-2Q53FS6
TRAP1	XM_011522345.3 link	c.499C>G	p.Arg167Gly	missense_variant	Exon 9 of 18		XP_011520647.1
LOC124903630	XR_007064950.1 link	n.-30G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10 link	c.919C>G	p.Arg307Gly	missense_variant	Exon 9 of 18	1	NM_016292.3	ENSP00000246957.5		Q12931-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55038

AN:

151970

Hom.:

11463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.444

AC:

111341

AN:

250516

AF XY:

0.450

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.445

GnomAD4 exome

AF:

0.429

AC:

626767

AN:

1461452

Hom.:

137630

Cov.:

AF XY:

0.433

AC XY:

314668

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.139

AC:

4637

AN:

33480

American (AMR)

AF:

0.462

AC:

20621

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

12603

AN:

26132

East Asian (EAS)

AF:

0.480

AC:

19068

AN:

39688

South Asian (SAS)

AF:

0.520

AC:

44877

AN:

86240

European-Finnish (FIN)

AF:

0.517

AC:

27506

AN:

53244

Middle Eastern (MID)

AF:

0.394

AC:

2271

AN:

5766

European-Non Finnish (NFE)

AF:

0.423

AC:

470007

AN:

1111868

Other (OTH)

AF:

0.417

AC:

25177

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21182

42364

63547

84729

105911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14370

28740

43110

57480

71850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

55052

AN:

152088

Hom.:

11462

Cov.:

AF XY:

0.372

AC XY:

27659

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.144

AC:

5995

AN:

41506

American (AMR)

AF:

0.435

AC:

6643

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1670

AN:

3470

East Asian (EAS)

AF:

0.530

AC:

2728

AN:

5152

South Asian (SAS)

AF:

0.529

AC:

2553

AN:

4830

European-Finnish (FIN)

AF:

0.525

AC:

5549

AN:

10576

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28622

AN:

67962

Other (OTH)

AF:

0.378

AC:

797

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1735

3470

5204

6939

8674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.381

Hom.:

3650

Bravo

AF:

0.342

TwinsUK

AF:

0.407

AC:

1511

ALSPAC

AF:

0.426

AC:

1640

ESP6500AA

AF:

0.146

AC:

643

ESP6500EA

AF:

0.426

AC:

3667

ExAC

AF:

0.436

AC:

52923

Asia WGS

AF:

0.486

AC:

1692

AN:

3478

EpiCase

AF:

0.410

EpiControl

AF:

0.416

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.76

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.047

T;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.062

T;T;T;T

MetaRNN

Benign

0.000029

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.1

N;.;.;.

PhyloP100

0.015

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.020

N;.;N;.

REVEL

Benign

0.022

Sift

Benign

0.34

T;.;T;.

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.053

MPC

0.019

ClinPred

0.0069

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.56

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over