Genetic Variant TSEN15:p.Pro11Ser (chr1-184051786-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052965.4(TSEN15):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSEN15
NM_052965.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0899578).

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.31C>T	p.Pro11Ser	missense	Exon 1 of 5	NP_443197.1	Q8WW01-1
TSEN15	NM_001300764.2		c.31C>T	p.Pro11Ser	missense	Exon 1 of 5	NP_001287693.1	A0A2U3TZM3
TSEN15	NM_001363643.2		c.31C>T	p.Pro11Ser	missense	Exon 1 of 4	NP_001350572.1	A0A2R8YDU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSEN15	ENST00000645668.2	MANE Select	c.31C>T	p.Pro11Ser	missense	Exon 1 of 5	ENSP00000493902.2	Q8WW01-1
TSEN15	ENST00000361641.6	TSL:1	c.31C>T	p.Pro11Ser	missense	Exon 1 of 5	ENSP00000355299.2	A0A2U3TZM3
TSEN15	ENST00000462677.3	TSL:1	n.31C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000432397.2	H0YCV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1368034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674478

African (AFR)

AF:

0.00

AC:

AN:

29276

American (AMR)

AF:

0.00

AC:

AN:

34056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24410

East Asian (EAS)

AF:

0.00

AC:

AN:

33392

South Asian (SAS)

AF:

0.00

AC:

AN:

76516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066598

Other (OTH)

AF:

0.00

AC:

AN:

56842

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.65

M_CAP

Benign

0.011

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.29

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.2

REVEL

Benign

0.055

Sift

Benign

0.21

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.058

MutPred

0.12

Gain of glycosylation at P11 (P = 0.0219)

MVP

0.10

MPC

0.49

ClinPred

0.073

GERP RS

1.9

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over