16-3692347-C-T

Variant names:

• chr16-3692347-C-T
• rs36099109
• NM_016292.3:c.89-1362G>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.89-1362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,754 control chromosomes in the GnomAD database, including 3,927 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 (3927 hom., cov: 30)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAP1	NM_016292.3	c.89-1362G>A		intron_variant	Intron 1 of 17	ENST00000246957.10	NP_057376.2
TRAP1	NM_001272049.2	c.89-3210G>A		intron_variant	Intron 1 of 16		NP_001258978.1
TRAP1	XM_011522345.3	c.-332-1362G>A		intron_variant	Intron 1 of 17		XP_011520647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10	c.89-1362G>A		intron_variant	Intron 1 of 17	1	NM_016292.3	ENSP00000246957.5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32641 AN: 151638 Hom.: 3917 Cov.: 30

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.215 AC: 32691 AN: 151754 Hom.: 3927 Cov.: 30 AF XY: 0.214 AC XY: 15851 AN XY: 74134

African (AFR) AF: 0.330 AC: 13659 AN: 41346

American (AMR) AF: 0.161 AC: 2452 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1101 AN: 5090

South Asian (SAS) AF: 0.171 AC: 821 AN: 4808

European-Finnish (FIN) AF: 0.126 AC: 1336 AN: 10582

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11902 AN: 67914

Other (OTH) AF: 0.207 AC: 436 AN: 2104

Alfa AF: 0.0853 Hom.: 112

Bravo AF: 0.222

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.96
PhyloP100		0.38
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: rs36099109; hg19: chr16-3742348;