1-186335166-C-T

Variant summary

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

The NM_003292.3(TPR):c.4912-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,582,326 control chromosomes in the GnomAD database, including 11,183 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 0.091 (965 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10218 hom.)
• Consequence: TPR NM_003292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

Genes affected

TPR (HGNC:12017): (translocated promoter region, nuclear basket protein) This gene encodes a large coiled-coil protein that forms intranuclear filaments attached to the inner surface of nuclear pore complexes (NPCs). The protein directly interacts with several components of the NPC. It is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of this gene with several different kinase genes occur in some neoplasias. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPR	NM_003292.3	c.4912-37G>A		intron_variant		ENST00000367478.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPR	ENST00000367478.9	c.4912-37G>A		intron_variant		1	NM_003292.3	P1

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13897 AN: 151958 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.119 AC: 27100 AN: 227244 Hom.: 2332 AF XY: 0.120 AC XY: 14863 AN XY: 123728

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.0876

Gnomad ASJ exome AF: 0.0934

Gnomad EAS exome AF: 0.397

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0991

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.106 AC: 151759 AN: 1430250 Hom.: 10218 Cov.: 29 AF XY: 0.106 AC XY: 75492 AN XY: 710172

Gnomad4 AFR exome AF: 0.0259

Gnomad4 AMR exome AF: 0.0887

Gnomad4 ASJ exome AF: 0.0877

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0977

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0913 AC: 13890 AN: 152076 Hom.: 965 Cov.: 32 AF XY: 0.0954 AC XY: 7091 AN XY: 74328

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0964 Hom.: 933

Bravo AF: 0.0880

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.68

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: rs3817586; hg19: chr1-186304298; COSMIC: COSV66601622; COSMIC: COSV66601622;