NM_207346.3:c.1447C>G

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.1447C>G(p.Pro483Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,614,172 control chromosomes in the GnomAD database, including 3,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P483Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.049 ( 288 hom., cov: 33)

Exomes 𝑓: 0.064 ( 3279 hom. )

Consequence

TSEN54
NM_207346.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 7.51

Publications

18 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 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pontocerebellar hypoplasia type 4
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 (MetaRNN=0.00473243).

BP6

Variant 17-75524278-C-G is Benign according to our data. Variant chr17-75524278-C-G is described in ClinVar as Benign. ClinVar VariationId is 137759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	NM_207346.3	MANE Select	c.1447C>G	p.Pro483Ala	missense	Exon 11 of 11	NP_997229.2	Q7Z6J9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.1447C>G	p.Pro483Ala	missense	Exon 11 of 11	ENSP00000327487.6	Q7Z6J9-1
TSEN54	ENST00000680999.1		c.1660C>G	p.Pro554Ala	missense	Exon 11 of 11	ENSP00000504984.1	A0A7P0Z413
TSEN54	ENST00000915433.1		c.1603C>G	p.Pro535Ala	missense	Exon 11 of 11	ENSP00000585492.1

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

7488

AN:

152212

Hom.:

288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0817

Gnomad FIN

AF:

0.0687

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0681

Gnomad OTH

AF:

0.0526

GnomAD2 exomes

AF:

0.0590

AC:

14836

AN:

251384

AF XY:

0.0625

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.0570

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.0756

Gnomad NFE exome

AF:

0.0682

Gnomad OTH exome

AF:

0.0634

GnomAD4 exome

AF:

0.0640

AC:

93599

AN:

1461842

Hom.:

3279

Cov.:

AF XY:

0.0651

AC XY:

47338

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0102

AC:

343

AN:

33480

American (AMR)

AF:

0.0541

AC:

2419

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

1452

AN:

26136

East Asian (EAS)

AF:

0.000353

AC:

AN:

39700

South Asian (SAS)

AF:

0.0836

AC:

7212

AN:

86256

European-Finnish (FIN)

AF:

0.0743

AC:

3965

AN:

53384

Middle Eastern (MID)

AF:

0.0794

AC:

458

AN:

5768

European-Non Finnish (NFE)

AF:

0.0665

AC:

73985

AN:

1112000

Other (OTH)

AF:

0.0621

AC:

3751

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5593

11186

16778

22371

27964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2698

5396

8094

10792

13490

<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:

0.0492

AC:

7490

AN:

152330

Hom.:

288

Cov.:

AF XY:

0.0498

AC XY:

3712

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0114

AC:

474

AN:

41570

American (AMR)

AF:

0.0549

AC:

840

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3472

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0826

AC:

399

AN:

4828

European-Finnish (FIN)

AF:

0.0687

AC:

730

AN:

10620

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0681

AC:

4634

AN:

68024

Other (OTH)

AF:

0.0520

AC:

110

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0505

Hom.:

Bravo

AF:

0.0457

TwinsUK

AF:

0.0620

AC:

230

ALSPAC

AF:

0.0667

AC:

257

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.0655

AC:

563

ExAC

AF:

0.0585

AC:

7097

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.0706

EpiControl

AF:

0.0690

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Pontocerebellar hypoplasia type 2A (1)

Pontocerebellar hypoplasia type 4 (1)

Pontocerebellar hypoplasia type 5 (1)

Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

PhyloP100

7.5

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.34

MPC

0.90

ClinPred

0.016

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.66

Mutation Taster

=44/56

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over