Variant 19-54191871-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001077446.4(TSEN34):c.394G>A(p.Gly132Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,614,166 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 3 hom. )

Consequence

TSEN34
NM_001077446.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.52

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052583218).

BP6

Variant 19-54191871-G-A is Benign according to our data. Variant chr19-54191871-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 196514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	NM_001077446.4 linkuse as main transcript	c.394G>A	p.Gly132Arg	missense_variant	2/4	ENST00000396388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000396388.3 linkuse as main transcript	c.394G>A	p.Gly132Arg	missense_variant	2/4	1	NM_001077446.4	P2

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000714

AC:

178

AN:

249320

Hom.:

AF XY:

0.000857

AC XY:

116

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000812

AC:

1187

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

675

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000756

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000519

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000631

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.000485

AC:

ExAC

AF:

0.000827

AC:

100

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 23, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 27, 2015	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 05, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0072

.;T;T;.;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.59

M_CAP

Benign

0.023

MetaRNN

Benign

0.0053

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

.;.;L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.66

N;N;N;.;N;N

REVEL

Benign

0.076

Sift

Benign

0.37

T;T;T;.;T;T

Sift4G

Benign

0.39

T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;B;B

Vest4

0.28, 0.37, 0.28, 0.27

MutPred

0.26

Gain of MoRF binding (P = 0.0075);.;Gain of MoRF binding (P = 0.0075);.;Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);

MVP

0.64

MPC

0.35

ClinPred

0.0074

GERP RS

3.3

Varity_R

0.035

gMVP

0.37

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