ENST00000434205:c.-196A>C

Variant names:

• chr17-75516273-A-C
• rs62088462
• ENST00000434205:c.-196A>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000434205(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 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000434205	c.-196A>C		5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000406559.4
TSEN54	ENST00000679370.1	n.330A>C		non_coding_transcript_exon_variant	Exon 1 of 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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;