NM_016292.3:c.2052C>T

Variant names:

• chr16-3658192-G-A
• rs1059857
• NM_016292.3:c.2052C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016292.3(TRAP1):​c.2052C>T​(p.Asp684Asp) 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, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.09
• Publications: 10 publications found

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]

DNASE1 Gene-Disease associations (from GenCC):

• autosomal systemic lupus erythematosus type 16

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	NM_016292.3	MANE Select	c.2052C>T	p.Asp684Asp	synonymous	Exon 18 of 18	NP_057376.2	Q12931-1
	TRAP1	NM_001272049.2		c.1893C>T	p.Asp631Asp	synonymous	Exon 17 of 17	NP_001258978.1	Q12931-2
	DNASE1	NM_001387140.1		c.*21+325G>A		intron	N/A	NP_001374069.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	ENST00000246957.10	TSL:1 MANE Select	c.2052C>T	p.Asp684Asp	synonymous	Exon 18 of 18	ENSP00000246957.5	Q12931-1
	TRAP1	ENST00000575671.5	TSL:1	c.1425C>T	p.Asp475Asp	synonymous	Exon 13 of 13	ENSP00000458166.1	I3L0K7
	DNASE1	ENST00000407479.5	TSL:1	c.*239G>A		3_prime_UTR	Exon 10 of 10	ENSP00000385905.1	P24855-1

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

GnomAD2 exomes AF: 0.0571 AC: 14345 AN: 251366 AF XY: 0.0570

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 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

African (AFR) AF: 0.194 AC: 6487 AN: 33468

American (AMR) AF: 0.0268 AC: 1197 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0350 AC: 914 AN: 26132

East Asian (EAS) AF: 0.0455 AC: 1805 AN: 39700

South Asian (SAS) AF: 0.0965 AC: 8318 AN: 86240

European-Finnish (FIN) AF: 0.0640 AC: 3413 AN: 53364

Middle Eastern (MID) AF: 0.0439 AC: 253 AN: 5766

European-Non Finnish (NFE) AF: 0.0430 AC: 47816 AN: 1111824

Other (OTH) AF: 0.0564 AC: 3403 AN: 60386

GnomAD4 genome AF: 0.0855 AC: 12994 AN: 152050 Hom.: 839 Cov.: 32 AF XY: 0.0853 AC XY: 6338 AN XY: 74332

African (AFR) AF: 0.188 AC: 7776 AN: 41446

American (AMR) AF: 0.0421 AC: 644 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.0366 AC: 189 AN: 5168

South Asian (SAS) AF: 0.0986 AC: 475 AN: 4818

European-Finnish (FIN) AF: 0.0661 AC: 697 AN: 10552

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0425 AC: 2891 AN: 67996

Other (OTH) AF: 0.0745 AC: 157 AN: 2108

Alfa AF: 0.0609 Hom.: 1019

Bravo AF: 0.0871

Asia WGS AF: 0.0810 AC: 282 AN: 3478

EpiCase AF: 0.0429

EpiControl AF: 0.0382

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-1.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1059857; hg19: chr16-3708193;