16-3676159-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016292.3(TRAP1):c.705-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,611,058 control chromosomes in the GnomAD database, including 665,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66318 hom., cov: 32)

Exomes 𝑓: 0.91 ( 598976 hom. )

Consequence

TRAP1
NM_016292.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.548

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:

LOC124903630 (HGNC:):

LOC124903630 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-3676159-A-G is Benign according to our data. Variant chr16-3676159-A-G is described in ClinVar as [Benign]. Clinvar id is 260709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRAP1	NM_016292.3 link	c.705-14T>C	intron_variant	Intron 6 of 17	ENST00000246957.10	NP_057376.2	Q12931-1A0A140VJY2
TRAP1	NM_001272049.2 link	c.546-14T>C	intron_variant	Intron 5 of 16		NP_001258978.1	Q12931-2Q53FS6
TRAP1	XM_011522345.3 link	c.285-14T>C	intron_variant	Intron 6 of 17		XP_011520647.1
LOC124903630	XR_007064950.1 link	n.1666A>G	non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10 link	c.705-14T>C		intron_variant	Intron 6 of 17	1	NM_016292.3	ENSP00000246957.5		Q12931-1

Frequencies

GnomAD3 genomes

AF:

0.932

AC:

141829

AN:

152166

Hom.:

66255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.981

Gnomad AMI

AF:

0.951

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.948

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.981

Gnomad FIN

AF:

0.916

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.893

Gnomad OTH

AF:

0.928

GnomAD3 exomes

AF:

0.932

AC:

231876

AN:

248890

Hom.:

108231

AF XY:

0.931

AC XY:

125370

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.983

Gnomad AMR exome

AF:

0.960

Gnomad ASJ exome

AF:

0.941

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.983

Gnomad FIN exome

AF:

0.911

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.924

GnomAD4 exome

AF:

0.906

AC:

1321041

AN:

1458774

Hom.:

598976

Cov.:

AF XY:

0.908

AC XY:

658997

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.985

Gnomad4 AMR exome

AF:

0.957

Gnomad4 ASJ exome

AF:

0.940

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.982

Gnomad4 FIN exome

AF:

0.907

Gnomad4 NFE exome

AF:

0.890

Gnomad4 OTH exome

AF:

0.920

GnomAD4 genome

AF:

0.932

AC:

141951

AN:

152284

Hom.:

66318

Cov.:

AF XY:

0.935

AC XY:

69584

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.981

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.948

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.981

Gnomad4 FIN

AF:

0.916

Gnomad4 NFE

AF:

0.893

Gnomad4 OTH

AF:

0.929

Alfa

AF:

0.916

Hom.:

12160

Bravo

AF:

0.936

Asia WGS

AF:

0.990

AC:

3442

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.7

DANN

Benign

0.55

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