17-75516282-C-T

Variant summary

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

The ENST00000434205.8(TSEN54):c.-187C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 180,924 control chromosomes in the GnomAD database, including 3,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3361 hom., cov: 33)
  • Exomes 𝑓: 0.12 (235 hom.)
• Consequence: TSEN54 ENST00000434205.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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 17-75516282-C-T is Benign according to our data. Variant chr17-75516282-C-T is described in ClinVar as [Benign]. Clinvar id is 1295937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 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.-187C>T		5_prime_UTR_variant	1/10	5
TSEN54	ENST00000679370.1	n.339C>T		non_coding_transcript_exon_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28067 AN: 152016 Hom.: 3351 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.122 AC: 3501 AN: 28790 Hom.: 235 Cov.: 3 AF XY: 0.120 AC XY: 1876 AN XY: 15626

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.0901

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0915

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.185 AC: 28114 AN: 152134 Hom.: 3361 Cov.: 33 AF XY: 0.181 AC XY: 13472 AN XY: 74408

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.179

Alfa AF: 0.168 Hom.: 333

Bravo AF: 0.192

Asia WGS AF: 0.0890 AC: 313 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 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.3
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72851941; hg19: chr17-73512363;