rs77247739

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1166A>C(p.Gln389Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 1,547,262 control chromosomes in the GnomAD database, including 7,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q389H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.093 ( 711 hom., cov: 32)

Exomes 𝑓: 0.095 ( 6631 hom. )

Consequence

TSEN54
NM_207346.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.412

Publications

15 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 (MetaRNN=0.0018183887).

BP6

Variant 17-75522247-A-C is Benign according to our data. Variant chr17-75522247-A-C is described in ClinVar as Benign. ClinVar VariationId is 96672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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.1166A>C	p.Gln389Pro	missense	Exon 8 of 11	NP_997229.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.1166A>C	p.Gln389Pro	missense	Exon 8 of 11	ENSP00000327487.6
TSEN54	ENST00000680999.1		c.1166A>C	p.Gln389Pro	missense	Exon 8 of 11	ENSP00000504984.1
TSEN54	ENST00000915433.1		c.1166A>C	p.Gln389Pro	missense	Exon 8 of 11	ENSP00000585492.1

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14199

AN:

152154

Hom.:

707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0751

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.0796

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0937

GnomAD2 exomes

AF:

0.0778

AC:

11366

AN:

146068

AF XY:

0.0778

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.0758

Gnomad EAS exome

AF:

0.000748

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0835

GnomAD4 exome

AF:

0.0946

AC:

131976

AN:

1394990

Hom.:

6631

Cov.:

AF XY:

0.0938

AC XY:

64468

AN XY:

687646

show subpopulations

African (AFR)

AF:

0.112

AC:

3516

AN:

31528

American (AMR)

AF:

0.0527

AC:

1881

AN:

35720

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

1933

AN:

25136

East Asian (EAS)

AF:

0.000505

AC:

AN:

35660

South Asian (SAS)

AF:

0.0680

AC:

5379

AN:

79146

European-Finnish (FIN)

AF:

0.0845

AC:

3982

AN:

47126

Middle Eastern (MID)

AF:

0.0750

AC:

397

AN:

5290

European-Non Finnish (NFE)

AF:

0.102

AC:

110011

AN:

1077556

Other (OTH)

AF:

0.0840

AC:

4859

AN:

57828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7770

15539

23309

31078

38848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3976

7952

11928

15904

19880

<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:

0.0934

AC:

14217

AN:

152272

Hom.:

711

Cov.:

AF XY:

0.0910

AC XY:

6777

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.109

AC:

4522

AN:

41566

American (AMR)

AF:

0.0749

AC:

1146

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.0696

AC:

336

AN:

4828

European-Finnish (FIN)

AF:

0.0796

AC:

845

AN:

10616

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6892

AN:

67998

Other (OTH)

AF:

0.0937

AC:

198

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

664

1328

1993

2657

3321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0856

Hom.:

322

Bravo

AF:

0.0924

TwinsUK

AF:

0.105

AC:

390

ALSPAC

AF:

0.0965

AC:

372

ESP6500AA

AF:

0.0733

AC:

290

ESP6500EA

AF:

0.0677

AC:

522

ExAC

AF:

0.0333

AC:

2844

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

5.8

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.016

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.41

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.067

Sift

Benign

0.17

Sift4G

Benign

0.24

Polyphen

0.13

Vest4

0.068

MPC

0.35

ClinPred

0.0039

GERP RS

-0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.65

Mutation Taster

=97/3

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