16-3687374-T-C

Position:

• chr16-3687374-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

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]

ENSG00000276754 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAP1	NM_016292.3	c.331-1238A>G		intron_variant		ENST00000246957.10	NP_057376.2
TRAP1	NM_001272049.2	c.172-1238A>G		intron_variant			NP_001258978.1
TRAP1	XM_011522345.3	c.-90-1238A>G		intron_variant			XP_011520647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10	c.331-1238A>G		intron_variant		1	NM_016292.3	ENSP00000246957.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33767 AN: 151974 Hom.: 3822 Cov.: 31

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: 26 AN: 84 Hom.: 2 Cov.: 0 AF XY: 0.370 AC XY: 20 AN XY: 54

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.222 AC: 33818 AN: 152092 Hom.: 3835 Cov.: 31 AF XY: 0.222 AC XY: 16533 AN XY: 74370

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.247

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs79848897; hg19: chr16-3737375;