16-3696240-C-T

Variant names:

• chr16-3696240-C-T
• rs6500550
• NM_016292.3:c.89-5255G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016292.3(TRAP1):​c.89-5255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,898 control chromosomes in the GnomAD database, including 16,781 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 0.43 (16781 hom., cov: 31)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 18 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]

TRAP1 Gene-Disease associations (from GenCC):

• syndromic disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 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.89-5255G>A		intron	N/A	NP_057376.2	Q12931-1
	TRAP1	NM_001272049.2		c.89-7103G>A		intron	N/A	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.89-5255G>A		intron	N/A	ENSP00000246957.5	Q12931-1
	TRAP1	ENST00000900180.1		c.89-5255G>A		intron	N/A	ENSP00000570239.1
	TRAP1	ENST00000923089.1		c.89-5255G>A		intron	N/A	ENSP00000593148.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65224 AN: 151780 Hom.: 16735 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65337 AN: 151898 Hom.: 16781 Cov.: 31 AF XY: 0.428 AC XY: 31775 AN XY: 74248

African (AFR) AF: 0.728 AC: 30155 AN: 41438

American (AMR) AF: 0.351 AC: 5353 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1112 AN: 3466

East Asian (EAS) AF: 0.391 AC: 2023 AN: 5172

South Asian (SAS) AF: 0.333 AC: 1600 AN: 4806

European-Finnish (FIN) AF: 0.295 AC: 3108 AN: 10538

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20681 AN: 67914

Other (OTH) AF: 0.415 AC: 876 AN: 2112

Alfa AF: 0.342 Hom.: 43479

Bravo AF: 0.449

Asia WGS AF: 0.411 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.28
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6500550; hg19: chr16-3746241;