rs6501820

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207346.3(TSEN54):c.1122G>C(p.Arg374Arg) 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:15

Conservation

PhyloP100: 0.0780

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 2A
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
pontocerebellar hypoplasia type 4
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
pontocerebellar hypoplasia type 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 96670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TSEN54	NM_207346.3 link	c.1122G>C	p.Arg374Arg	synonymous_variant	Exon 8 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.1122G>C	p.Arg374Arg	synonymous_variant	Exon 8 of 11	1	NM_207346.3	ENSP00000327487.6		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

GnomAD2 exomes

AF:

0.814

AC:

127526

AN:

156712

AF XY:

0.829

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 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

African (AFR)

AF:

0.982

AC:

31006

AN:

31584

American (AMR)

AF:

0.563

AC:

20513

AN:

36414

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

20664

AN:

25112

East Asian (EAS)

AF:

0.513

AC:

18347

AN:

35746

South Asian (SAS)

AF:

0.891

AC:

70610

AN:

79274

European-Finnish (FIN)

AF:

0.887

AC:

42696

AN:

48156

Middle Eastern (MID)

AF:

0.927

AC:

5215

AN:

5628

European-Non Finnish (NFE)

AF:

0.910

AC:

980350

AN:

1077822

Other (OTH)

AF:

0.869

AC:

50347

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

8113

16227

24340

32454

40567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21056

42112

63168

84224

105280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.888

AC:

135185

AN:

152196

Hom.:

60900

Cov.:

AF XY:

0.882

AC XY:

65653

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.975

AC:

40532

AN:

41556

American (AMR)

AF:

0.703

AC:

10743

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

2898

AN:

3472

East Asian (EAS)

AF:

0.550

AC:

2833

AN:

5152

South Asian (SAS)

AF:

0.876

AC:

4225

AN:

4824

European-Finnish (FIN)

AF:

0.885

AC:

9382

AN:

10604

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.906

AC:

61605

AN:

67996

Other (OTH)

AF:

0.877

AC:

1851

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

721

1442

2163

2884

3605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Nov 12, 2013

Eurofins Ntd Llc (ga)

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

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

- -

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

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

- -

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

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.6

(source)

DANN

Benign

0.72

PhyloP100

0.078

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over