17-75516572-G-T

Variant names:

Variant summary

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

The NM_207346.3(TSEN54):c.12G>T(p.Glu4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,149,816 control chromosomes in the GnomAD database, including 271,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27373 hom., cov: 32)

Exomes 𝑓: 0.70 ( 243801 hom. )

Consequence

TSEN54
NM_207346.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -2.89

Variant links:

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]

TSEN54 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 (MetaRNN=4.9241294E-6).

BP6

Variant 17-75516572-G-T is Benign according to our data. Variant chr17-75516572-G-T is described in ClinVar as [Benign]. Clinvar id is 96673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75516572-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN54	NM_207346.3 link	c.12G>T	p.Glu4Asp	missense_variant	Exon 1 of 11	ENST00000333213.11	NP_997229.2	Q7Z6J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 link	c.12G>T	p.Glu4Asp	missense_variant	Exon 1 of 11	1	NM_207346.3	ENSP00000327487.6		Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

88376

AN:

149396

Hom.:

27379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.760

AC:

AN:

104

Hom.:

AF XY:

0.719

AC XY:

AN XY:

show subpopulations

Gnomad NFE exome

AF:

0.760

GnomAD4 exome

AF:

0.696

AC:

695858

AN:

1000312

Hom.:

243801

Cov.:

AF XY:

0.697

AC XY:

328210

AN XY:

470990

show subpopulations

Gnomad4 AFR exome

AF:

0.398

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.702

Gnomad4 NFE exome

AF:

0.710

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.591

AC:

88389

AN:

149504

Hom.:

27373

Cov.:

AF XY:

0.590

AC XY:

43055

AN XY:

72966

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.603

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.688

Gnomad4 FIN

AF:

0.695

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.562

Hom.:

2148

Bravo

AF:

0.566

ExAC

AF:

0.259

AC:

181

Asia WGS

AF:

0.599

AC:

1827

AN:

3054

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 22, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 24, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pontocerebellar hypoplasia type 2A

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pontoneocerebellar hypoplasia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Pontocerebellar hypoplasia type 5

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pontocerebellar hypoplasia type 4

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.043

DANN

Benign

0.80

DEOGEN2

Benign

0.0099

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0000049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.18

REVEL

Benign

0.059

Sift

Benign

0.30

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.022

MutPred

0.15

Loss of glycosylation at P3 (P = 0.0618);

MPC

0.23

ClinPred

0.087

GERP RS

-8.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.14

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