1-184054395-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052965.4(TSEN15):​c.177A>T​(p.Gln59His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TSEN15
NM_052965.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3082083).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSEN15NM_052965.4 linkc.177A>T p.Gln59His missense_variant 2/5 ENST00000645668.2 NP_443197.1 Q8WW01-1B1ALV0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSEN15ENST00000645668.2 linkc.177A>T p.Gln59His missense_variant 2/5 NM_052965.4 ENSP00000493902.2 Q8WW01-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250454
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135338
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456730
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
724956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.;.;.;.;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.70
T;T;T;T;T;T;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.31
T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.3
M;M;.;.;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-4.2
.;D;D;.;D;.;.
REVEL
Benign
0.094
Sift
Pathogenic
0.0
.;D;D;.;D;.;.
Sift4G
Uncertain
0.010
.;D;D;.;D;.;.
Polyphen
0.0020
B;.;.;.;.;.;.
Vest4
0.32, 0.15, 0.29
MutPred
0.30
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.42
MPC
0.48
ClinPred
0.48
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1046934; hg19: chr1-184023529; API