rs1059857

chr16-3658192-G-Achr16-3658192-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.09

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]

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	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	c.2052C>T	p.Asp684=	synonymous_variant	18/18	1	NM_016292.3	P1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12982 AN: 151932 Hom.: 838 Cov.: 32

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

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.: 34 AF XY: 0.0511 AC XY: 37147 AN XY: 727122

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.: 32 AF XY: 0.0853 AC XY: 6338 AN XY: 74332

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

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

Other links and lift over

dbSNP: rs1059857; hg19: chr16-3708193;