Genetic Variant TRAP1:c.331-1238A>G (chr16-3687374-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016292.3(TRAP1):c.331-1238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,176 control chromosomes in the GnomAD database, including 3,837 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3835 hom., cov: 31)

Exomes 𝑓: 0.31 ( 2 hom. )

Consequence

TRAP1
NM_016292.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.630

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

syndromic disease
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

TRAP1 links:

ENSG00000276754 (HGNC:):

ENSG00000276754 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 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.331-1238A>G		intron	N/A	NP_057376.2	Q12931-1
	TRAP1	NM_001272049.2		c.172-1238A>G		intron	N/A	NP_001258978.1	Q12931-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAP1	ENST00000246957.10	TSL:1 MANE Select	c.331-1238A>G	intron	N/A	ENSP00000246957.5	Q12931-1
TRAP1	ENST00000900180.1		c.331-1238A>G	intron	N/A	ENSP00000570239.1
TRAP1	ENST00000923089.1		c.331-1238A>G	intron	N/A	ENSP00000593148.1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33767

AN:

151974

Hom.:

3822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.310

AC:

AN:

Hom.:

Cov.:

AF XY:

0.370

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.293

AC:

AN:

Other (OTH)

AF:

0.417

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33818

AN:

152092

Hom.:

3835

Cov.:

AF XY:

0.222

AC XY:

16533

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.218

AC:

9038

AN:

41470

American (AMR)

AF:

0.217

AC:

3308

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

951

AN:

3470

East Asian (EAS)

AF:

0.339

AC:

1752

AN:

5162

South Asian (SAS)

AF:

0.276

AC:

1332

AN:

4830

European-Finnish (FIN)

AF:

0.156

AC:

1654

AN:

10586

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14875

AN:

67986

Other (OTH)

AF:

0.247

AC:

522

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1344

2688

4032

5376

6720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

182

Bravo

AF:

0.227

Asia WGS

AF:

0.325

AC:

1126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

(source)

DANN

Benign

0.48

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over