rs150169668

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_StrongBS1BS2

The NM_207346.3(TSEN54):c.1328C>G(p.Ser443Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,170 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 15 hom., cov: 32)

Exomes 𝑓: 0.013 ( 197 hom. )

Consequence

TSEN54
NM_207346.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.90

Publications

10 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=0.003773123).

BP6

Variant 17-75523677-C-G is Benign according to our data. Variant chr17-75523677-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0102 (1555/152296) while in subpopulation SAS AF = 0.0182 (88/4832). AF 95% confidence interval is 0.0151. There are 15 homozygotes in GnomAd4. There are 797 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	NM_207346.3	MANE Select	c.1328C>G	p.Ser443Cys	missense	Exon 10 of 11	NP_997229.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.1328C>G	p.Ser443Cys	missense	Exon 10 of 11	ENSP00000327487.6
TSEN54	ENST00000680999.1		c.1541C>G	p.Ser514Cys	missense	Exon 10 of 11	ENSP00000504984.1
TSEN54	ENST00000545228.3	TSL:5	c.1516C>G	p.Leu506Val	missense	Exon 10 of 11	ENSP00000438169.3

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1558

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0122

AC:

3065

AN:

251478

AF XY:

0.0133

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0134

AC:

19627

AN:

1461874

Hom.:

197

Cov.:

AF XY:

0.0136

AC XY:

9906

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00608

AC:

272

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00788

AC:

206

AN:

26136

East Asian (EAS)

AF:

0.000353

AC:

AN:

39700

South Asian (SAS)

AF:

0.0231

AC:

1991

AN:

86258

European-Finnish (FIN)

AF:

0.0236

AC:

1258

AN:

53414

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0135

AC:

14997

AN:

1112000

Other (OTH)

AF:

0.0130

AC:

783

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1194

2389

3583

4778

5972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.0102

AC:

1555

AN:

152296

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41560

American (AMR)

AF:

0.00948

AC:

145

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0182

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0245

AC:

260

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0130

AC:

881

AN:

68026

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0103

Hom.:

Bravo

AF:

0.00836

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.0115

AC:

1394

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0135

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.077

Eigen

Benign

0.15

Eigen_PC

Benign

0.059

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.3

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Benign

0.047

Sift4G

Benign

0.10

Polyphen

0.97

Vest4

0.10

MPC

0.67

ClinPred

0.016

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.29

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over