16-3658192-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016292.3(TRAP1):​c.2052C>A​(p.Asp684Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

TRAP1
NM_016292.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0301027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAP1NM_016292.3 linkc.2052C>A p.Asp684Glu missense_variant Exon 18 of 18 ENST00000246957.10 NP_057376.2 Q12931-1A0A140VJY2
DNASE1NM_005223.4 linkc.*239G>T downstream_gene_variant ENST00000246949.10 NP_005214.2 P24855-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRAP1ENST00000246957.10 linkc.2052C>A p.Asp684Glu missense_variant Exon 18 of 18 1 NM_016292.3 ENSP00000246957.5 Q12931-1
DNASE1ENST00000246949.10 linkc.*239G>T downstream_gene_variant 1 NM_005223.4 ENSP00000246949.5 P24855-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151968
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151968
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74222
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.0020
DANN
Benign
0.51
DEOGEN2
Benign
0.017
T;.;.
Eigen
Benign
-2.5
Eigen_PC
Benign
-2.5
FATHMM_MKL
Benign
0.085
N
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.080
N;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.58
N;.;N
REVEL
Benign
0.14
Sift
Benign
0.91
T;.;T
Sift4G
Benign
0.93
T;T;T
Polyphen
0.0010
B;.;.
Vest4
0.092
MutPred
0.37
Gain of solvent accessibility (P = 0.2601);.;.;
MVP
0.11
MPC
0.019
ClinPred
0.027
T
GERP RS
-11
Varity_R
0.12
gMVP
0.33

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.

Other links and lift over

dbSNP: rs1059857; hg19: chr16-3708193; API