NM_207346.3:c.285+32C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207346.3(TSEN54):c.285+32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,443,256 control chromosomes in the GnomAD database, including 351,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 24369 hom., cov: 29)

Exomes 𝑓: 0.72 ( 326830 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.00

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-75517104-C-A is Benign according to our data. Variant chr17-75517104-C-A is described in ClinVar as Benign. ClinVar VariationId is 160133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN54	NM_207346.3 link	c.285+32C>A		intron_variant	Intron 3 of 10	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.285+32C>A		intron_variant	Intron 3 of 10	1	NM_207346.3	ENSP00000327487.6		Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

79302

AN:

122580

Hom.:

24374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.676

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.640

GnomAD2 exomes

AF:

0.601

AC:

114087

AN:

189872

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.451

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.622

GnomAD4 exome

AF:

0.722

AC:

952874

AN:

1320614

Hom.:

326830

Cov.:

AF XY:

0.724

AC XY:

473894

AN XY:

654972

show subpopulations

African (AFR)

AF:

0.346

AC:

5577

AN:

16112

American (AMR)

AF:

0.437

AC:

15125

AN:

34638

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

15005

AN:

22748

East Asian (EAS)

AF:

0.482

AC:

17096

AN:

35468

South Asian (SAS)

AF:

0.720

AC:

54588

AN:

75846

European-Finnish (FIN)

AF:

0.730

AC:

34048

AN:

46616

Middle Eastern (MID)

AF:

0.688

AC:

3543

AN:

5150

European-Non Finnish (NFE)

AF:

0.748

AC:

770937

AN:

1030298

Other (OTH)

AF:

0.688

AC:

36955

AN:

53738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

16588

33177

49765

66354

82942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19322

38644

57966

77288

96610

<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:

0.647

AC:

79303

AN:

122642

Hom.:

24369

Cov.:

AF XY:

0.645

AC XY:

38841

AN XY:

60212

show subpopulations

African (AFR)

AF:

0.393

AC:

8141

AN:

20740

American (AMR)

AF:

0.531

AC:

7028

AN:

13234

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2078

AN:

3106

East Asian (EAS)

AF:

0.498

AC:

2341

AN:

4698

South Asian (SAS)

AF:

0.707

AC:

3117

AN:

4406

European-Finnish (FIN)

AF:

0.731

AC:

7272

AN:

9950

Middle Eastern (MID)

AF:

0.676

AC:

177

AN:

262

European-Non Finnish (NFE)

AF:

0.744

AC:

47255

AN:

63554

Other (OTH)

AF:

0.638

AC:

1139

AN:

1784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1593

3187

4780

6374

7967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.632

Hom.:

16290

Bravo

AF:

0.486

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely 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

- -

not provided

Benign:2

Jun 26, 2018

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

- -

Pontocerebellar hypoplasia type 2A

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.79

CADD

Benign

8.8

(source)

DANN

Benign

0.44

PhyloP100

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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