dbSNP rs193298754: TSEN15:p.Met49Thr (chr1-184054364-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_052965.4(TSEN15):c.146T>C(p.Met49Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000581 in 1,582,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

TSEN15
NM_052965.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38948908).

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	UniProt
TSEN15	NM_052965.4	MANE Select	c.146T>C	p.Met49Thr	missense	Exon 2 of 5	NP_443197.1	Q8WW01-1
TSEN15	NM_001300764.2		c.146T>C	p.Met49Thr	missense	Exon 2 of 5	NP_001287693.1	A0A2U3TZM3
TSEN15	NM_001363643.2		c.146T>C	p.Met49Thr	missense	Exon 2 of 4	NP_001350572.1	A0A2R8YDU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSEN15	ENST00000645668.2	MANE Select	c.146T>C	p.Met49Thr	missense	Exon 2 of 5	ENSP00000493902.2	Q8WW01-1
TSEN15	ENST00000361641.6	TSL:1	c.146T>C	p.Met49Thr	missense	Exon 2 of 5	ENSP00000355299.2	A0A2U3TZM3
TSEN15	ENST00000462677.3	TSL:1	n.146T>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000432397.2	H0YCV5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000453

AC:

AN:

242712

AF XY:

0.0000459

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000808

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000601

AC:

AN:

1430098

Hom.:

Cov.:

AF XY:

0.0000744

AC XY:

AN XY:

712278

show subpopulations

African (AFR)

AF:

0.0000609

AC:

AN:

32826

American (AMR)

AF:

0.0000234

AC:

AN:

42690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

39432

South Asian (SAS)

AF:

0.00

AC:

AN:

82266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000762

AC:

AN:

1088972

Other (OTH)

AF:

0.00

AC:

AN:

59312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000544

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.64

M_CAP

Benign

0.017

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

PhyloP100

4.2

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.90

MVP

0.75

MPC

0.80

ClinPred

0.28

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.73

gMVP

0.80

Mutation Taster

=43/57

disease causing

(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