rs6501820

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207346.3(TSEN54):c.1122G>C(p.Arg374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,549,836 control chromosomes in the GnomAD database, including 616,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60900 hom., cov: 33)

Exomes 𝑓: 0.89 ( 555413 hom. )

Consequence

TSEN54
NM_207346.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0780

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-75522203-G-C is Benign according to our data. Variant chr17-75522203-G-C is described in ClinVar as [Benign]. Clinvar id is 96670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75522203-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.078 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.1122G>C	p.Arg374=	synonymous_variant	8/11	ENST00000333213.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.1122G>C	p.Arg374=	synonymous_variant	8/11	1	NM_207346.3	P1	Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

135078

AN:

152078

Hom.:

60847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.975

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.906

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.814

AC:

127526

AN:

156712

Hom.:

54093

AF XY:

0.829

AC XY:

69265

AN XY:

83602

show subpopulations

Gnomad AFR exome

AF:

0.982

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.819

Gnomad EAS exome

AF:

0.526

Gnomad SAS exome

AF:

0.893

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.908

Gnomad OTH exome

AF:

0.844

GnomAD4 exome

AF:

0.887

AC:

1239748

AN:

1397640

Hom.:

555413

Cov.:

AF XY:

0.888

AC XY:

611569

AN XY:

688622

show subpopulations

Gnomad4 AFR exome

AF:

0.982

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.823

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.891

Gnomad4 FIN exome

AF:

0.887

Gnomad4 NFE exome

AF:

0.910

Gnomad4 OTH exome

AF:

0.869

GnomAD4 genome

AF:

0.888

AC:

135185

AN:

152196

Hom.:

60900

Cov.:

AF XY:

0.882

AC XY:

65653

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.975

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.835

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.876

Gnomad4 FIN

AF:

0.885

Gnomad4 NFE

AF:

0.906

Gnomad4 OTH

AF:

0.877

Alfa

AF:

0.896

Hom.:

19813

Bravo

AF:

0.872

Asia WGS

AF:

0.762

AC:

2650

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 12, 2013	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Pontocerebellar hypoplasia type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Pontoneocerebellar hypoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Pontocerebellar hypoplasia type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

Cadd

Benign

5.6

Dann

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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