rs13926

Variant names:

• chr16-3674464-G-C
• rs13926
• NM_016292.3:c.919C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-3674464-G-C
• chr16-3674464-G-T
• chr16-3674464-G-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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. R307S) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0150
• Publications: 34 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

LOC124903630 (HGNC:):

ACMG classification

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.

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.919C>G	p.Arg307Gly	missense	Exon 9 of 18	NP_057376.2	Q12931-1
	TRAP1	NM_001272049.2		c.760C>G	p.Arg254Gly	missense	Exon 8 of 17	NP_001258978.1	Q12931-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	ENST00000246957.10	TSL:1 MANE Select	c.919C>G	p.Arg307Gly	missense	Exon 9 of 18	ENSP00000246957.5	Q12931-1
	TRAP1	ENST00000575671.5	TSL:1	c.292C>G	p.Arg98Gly	missense	Exon 4 of 13	ENSP00000458166.1	I3L0K7
	TRAP1	ENST00000900180.1		c.919C>G	p.Arg307Gly	missense	Exon 9 of 18	ENSP00000570239.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55038 AN: 151970 Hom.: 11463 Cov.: 33

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

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.: 58 AF XY: 0.433 AC XY: 314668 AN XY: 727018

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

GnomAD4 genome AF: 0.362 AC: 55052 AN: 152088 Hom.: 11462 Cov.: 33 AF XY: 0.372 AC XY: 27659 AN XY: 74364

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.76
DANN	Benign	0.61
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.062	T
MetaRNN	Benign	0.000029	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.015
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.022
Sift	Benign	0.34	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.053
MPC		0.019
ClinPred		0.0069	T
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)

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

Other links and lift over

dbSNP: rs13926; hg19: chr16-3724465; COSMIC: COSV55915372; COSMIC: COSV55915372;