rs73998306

chr17-75521668-A-C

Variant summary

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

The NM_207346.3(TSEN54):c.624-37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,608,944 control chromosomes in the GnomAD database, including 1,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (871 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (846 hom.)
• Consequence: TSEN54 NM_207346.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0230

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=-0.8).
• BP6: Variant 17-75521668-A-C is Benign according to our data. Variant chr17-75521668-A-C is described in ClinVar as [Benign]. Clinvar id is 160137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN54	NM_207346.3	c.624-37A>C		intron_variant		ENST00000333213.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN54	ENST00000333213.11	c.624-37A>C		intron_variant		1	NM_207346.3	P1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9126 AN: 152028 Hom.: 867 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0494

GnomAD3 exomes AF: 0.0165 AC: 4094 AN: 248736 Hom.: 364 AF XY: 0.0121 AC XY: 1634 AN XY: 134782

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.00340

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000925

Gnomad OTH exome AF: 0.00981

GnomAD4 exome AF: 0.00655 AC: 9549 AN: 1456798 Hom.: 846 Cov.: 29 AF XY: 0.00567 AC XY: 4114 AN XY: 725000

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.00338

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000545

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000622

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0601 AC: 9144 AN: 152146 Hom.: 871 Cov.: 32 AF XY: 0.0583 AC XY: 4336 AN XY: 74404

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0489

Alfa AF: 0.0109 Hom.: 29

Bravo AF: 0.0690

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.6
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73998306; hg19: chr17-73517749;