1-184054395-A-C

Variant names:

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.177A>C(p.Gln59His) 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 1,603,524 control chromosomes in the GnomAD database, including 93,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6992 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86655 hom. )

Consequence

TSEN15
NM_052965.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.78

Publications

94 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=0.0030647218).

BP6

Variant 1-184054395-A-C is Benign according to our data. Variant chr1-184054395-A-C is described in ClinVar as Benign. ClinVar VariationId is 1284754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052965.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSEN15	NM_052965.4	MANE Select	c.177A>C	p.Gln59His	missense	Exon 2 of 5	NP_443197.1
TSEN15	NM_001300764.2		c.177A>C	p.Gln59His	missense	Exon 2 of 5	NP_001287693.1
TSEN15	NM_001363643.2		c.177A>C	p.Gln59His	missense	Exon 2 of 4	NP_001350572.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSEN15	ENST00000645668.2	MANE Select	c.177A>C	p.Gln59His	missense	Exon 2 of 5	ENSP00000493902.2
TSEN15	ENST00000361641.6	TSL:1	c.177A>C	p.Gln59His	missense	Exon 2 of 5	ENSP00000355299.2
TSEN15	ENST00000462677.3	TSL:1	n.177A>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000432397.2

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43936

AN:

151898

Hom.:

6993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.335

AC:

83944

AN:

250454

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.340

AC:

494027

AN:

1451508

Hom.:

86655

Cov.:

AF XY:

0.340

AC XY:

245664

AN XY:

722494

show subpopulations

African (AFR)

AF:

0.139

AC:

4652

AN:

33368

American (AMR)

AF:

0.300

AC:

13359

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5770

AN:

26042

East Asian (EAS)

AF:

0.459

AC:

18142

AN:

39550

South Asian (SAS)

AF:

0.331

AC:

28293

AN:

85582

European-Finnish (FIN)

AF:

0.415

AC:

22150

AN:

53342

Middle Eastern (MID)

AF:

0.296

AC:

1704

AN:

5756

European-Non Finnish (NFE)

AF:

0.345

AC:

380298

AN:

1103334

Other (OTH)

AF:

0.327

AC:

19659

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

14299

28598

42896

57195

71494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12090

24180

36270

48360

60450

<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:

0.289

AC:

43948

AN:

152016

Hom.:

6992

Cov.:

AF XY:

0.293

AC XY:

21784

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.151

AC:

6280

AN:

41480

American (AMR)

AF:

0.281

AC:

4297

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

759

AN:

3466

East Asian (EAS)

AF:

0.473

AC:

2445

AN:

5166

South Asian (SAS)

AF:

0.335

AC:

1611

AN:

4816

European-Finnish (FIN)

AF:

0.416

AC:

4377

AN:

10530

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23283

AN:

67962

Other (OTH)

AF:

0.281

AC:

593

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1533

3066

4600

6133

7666

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:

0.320

Hom.:

37836

Bravo

AF:

0.274

TwinsUK

AF:

0.347

AC:

1286

ALSPAC

AF:

0.352

AC:

1357

ESP6500AA

AF:

0.163

AC:

717

ESP6500EA

AF:

0.348

AC:

2989

ExAC

AF:

0.335

AC:

40650

Asia WGS

AF:

0.366

AC:

1276

AN:

3476

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

PhyloP100

1.8

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.094

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.0020

Vest4

0.32

MutPred

0.30

Gain of sheet (P = 0.0221)

MPC

0.48

ClinPred

0.066

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.72

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over