1-184051715-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000361641.6(TSEN15):c.-41C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,319,566 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (105 hom.)
• Consequence: TSEN15 ENST00000361641.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.475

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-184051715-C-A is Benign according to our data. Variant chr1-184051715-C-A is described in ClinVar as [Benign]. Clinvar id is 1282462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN15	NM_052965.4			upstream_gene_variant		ENST00000645668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN15	ENST00000645668.2			upstream_gene_variant			NM_052965.4	P3

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3908 AN: 152044 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00944 AC: 75 AN: 7946 Hom.: 2 AF XY: 0.00898 AC XY: 41 AN XY: 4566

Gnomad AFR exome AF: 0.0866

Gnomad AMR exome AF: 0.0169

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00325 AC: 3790 AN: 1167410 Hom.: 105 Cov.: 29 AF XY: 0.00312 AC XY: 1753 AN XY: 562584

Gnomad4 AFR exome AF: 0.0897

Gnomad4 AMR exome AF: 0.00965

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.0000734

Gnomad4 SAS exome AF: 0.00632

Gnomad4 FIN exome AF: 0.000359

Gnomad4 NFE exome AF: 0.000896

Gnomad4 OTH exome AF: 0.00835

GnomAD4 genome AF: 0.0258 AC: 3930 AN: 152156 Hom.: 148 Cov.: 32 AF XY: 0.0252 AC XY: 1877 AN XY: 74370

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.0294

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs61738771; hg19: chr1-184020849;