Variant 19-54191295-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000302937.8(TSEN34):c.-4-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,544,452 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 16 hom. )

Consequence

TSEN34
ENST00000302937.8 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.655

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-54191295-G-A is Benign according to our data. Variant chr19-54191295-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 679020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	NM_001077446.4 linkuse as main transcript			upstream_gene_variant		ENST00000396388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000396388.3 linkuse as main transcript			upstream_gene_variant		1	NM_001077446.4	P2

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00138

AC:

1920

AN:

1392260

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1004

AN XY:

686752

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.000400

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00507

Gnomad4 FIN exome

AF:

0.0203

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000954

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152192

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000567

Asia WGS

AF:

0.00145

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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

-0.82

CADD

Benign

4.2

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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