Genetic Variant TSEN34:c.-4-158G>T (chr19-54191203-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282333.2(TSEN34):c.-4-158G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,384,726 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 53 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 369 hom. )

Consequence

TSEN34
NM_001282333.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.88

Variant links:

Genes affected

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

TSEN34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-54191203-G-T is Benign according to our data. Variant chr19-54191203-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34	NM_001077446.4 link	c.-162G>T		upstream_gene_variant		ENST00000396388.3	NP_001070914.1	Q9BSV6A0A024R4N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000396388.3 link	c.-162G>T		upstream_gene_variant		1	NM_001077446.4	ENSP00000379671.2		Q9BSV6

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1973

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.00851

Gnomad FIN

AF:

0.0304

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.0125

GnomAD4 exome

AF:

0.00565

AC:

6971

AN:

1232826

Hom.:

369

Cov.:

AF XY:

0.00556

AC XY:

3327

AN XY:

597898

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.00324

Gnomad4 FIN exome

AF:

0.0278

Gnomad4 NFE exome

AF:

0.000352

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0131

AC:

1983

AN:

151900

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1096

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.00852

Gnomad4 FIN

AF:

0.0304

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over