17-75516273-A-C

Variant summary

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

The ENST00000434205.8(TSEN54):c.-196A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 176,450 control chromosomes in the GnomAD database, including 8,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (8517 hom., cov: 34)
  • Exomes 𝑓: 0.17 (364 hom.)
• Consequence: TSEN54 ENST00000434205.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

Genes affected

TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-75516273-A-C is Benign according to our data. Variant chr17-75516273-A-C is described in ClinVar as [Benign]. Clinvar id is 667571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN54	ENST00000434205.8	c.-196A>C		5_prime_UTR_variant	1/10	5
TSEN54	ENST00000679370.1	n.330A>C		non_coding_transcript_exon_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44397 AN: 151912 Hom.: 8483 Cov.: 34

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.169 AC: 4128 AN: 24420 Hom.: 364 Cov.: 2 AF XY: 0.167 AC XY: 2230 AN XY: 13346

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.0148

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.293 AC: 44489 AN: 152030 Hom.: 8517 Cov.: 34 AF XY: 0.287 AC XY: 21368 AN XY: 74336

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.283

Alfa AF: 0.259 Hom.: 787

Bravo AF: 0.306

Asia WGS AF: 0.153 AC: 535 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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.1
Dann	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62088462; hg19: chr17-73512354;