rs2274432

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_052965.4(TSEN15):c.56G>A(p.Gly19Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,539,678 control chromosomes in the GnomAD database, including 89,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6955 hom., cov: 32)

Exomes 𝑓: 0.34 ( 82098 hom. )

Consequence

TSEN15
NM_052965.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.161

Publications

76 publications found

Variant links:

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

TSEN15 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 2F
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN15 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=1.4963746E-4).

BP6

Variant 1-184051811-G-A is Benign according to our data. Variant chr1-184051811-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN15	NM_052965.4 link	c.56G>A	p.Gly19Asp	missense_variant	Exon 1 of 5	ENST00000645668.2	NP_443197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN15	ENST00000645668.2 link	c.56G>A	p.Gly19Asp	missense_variant	Exon 1 of 5		NM_052965.4	ENSP00000493902.2

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43806

AN:

151964

Hom.:

6956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.332

AC:

46256

AN:

139146

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.340

AC:

471744

AN:

1387596

Hom.:

82098

Cov.:

AF XY:

0.340

AC XY:

232462

AN XY:

684630

show subpopulations

African (AFR)

AF:

0.139

AC:

4267

AN:

30742

American (AMR)

AF:

0.298

AC:

10532

AN:

35372

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5548

AN:

24936

East Asian (EAS)

AF:

0.452

AC:

15802

AN:

34966

South Asian (SAS)

AF:

0.333

AC:

25964

AN:

78014

European-Finnish (FIN)

AF:

0.412

AC:

18582

AN:

45090

Middle Eastern (MID)

AF:

0.295

AC:

1650

AN:

5592

European-Non Finnish (NFE)

AF:

0.345

AC:

370619

AN:

1075266

Other (OTH)

AF:

0.326

AC:

18780

AN:

57618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16901

33802

50703

67604

84505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12024

24048

36072

48096

60120

<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:

0.288

AC:

43818

AN:

152082

Hom.:

6955

Cov.:

AF XY:

0.292

AC XY:

21726

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.152

AC:

6305

AN:

41540

American (AMR)

AF:

0.280

AC:

4283

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3470

East Asian (EAS)

AF:

0.472

AC:

2423

AN:

5130

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4824

European-Finnish (FIN)

AF:

0.414

AC:

4383

AN:

10576

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.341

AC:

23139

AN:

67936

Other (OTH)

AF:

0.281

AC:

593

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1540

3079

4619

6158

7698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.328

Hom.:

33294

Bravo

AF:

0.273

TwinsUK

AF:

0.347

AC:

1287

ALSPAC

AF:

0.352

AC:

1356

ESP6500AA

AF:

0.136

AC:

552

ESP6500EA

AF:

0.296

AC:

2369

ExAC

AF:

0.220

AC:

19829

Asia WGS

AF:

0.366

AC:

1278

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18391951) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

T;.;.;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.56

T;T;T;T;T;T;T

MetaRNN

Benign

0.00015

T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

L;L;.;.;.;.;.

PhyloP100

-0.16

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

.;N;N;.;N;.;.

REVEL

Benign

0.16

Sift

Benign

0.035

.;D;T;.;T;.;.

Sift4G

Uncertain

0.022

.;D;D;.;D;.;.

Polyphen

0.0

B;.;.;.;.;.;.

Vest4

0.14, 0.072, 0.13

MPC

0.75

ClinPred

0.0038

GERP RS

-1.6

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.18

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

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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