chr1-184051811-G-A

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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6955 hom., cov: 32)
Exomes 𝑓: 0.34 ( 82098 hom. )

Consequence

TSEN15
NM_052965.4 missense

Scores

3
15

Clinical Significance

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

Conservation

PhyloP100: -0.161
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]

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 id is 1249884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-184051811-G-A is described in Lovd as [Benign].
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
TSEN15NM_052965.4 linkc.56G>A p.Gly19Asp missense_variant Exon 1 of 5 ENST00000645668.2 NP_443197.1 Q8WW01-1B1ALV0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSEN15ENST00000645668.2 linkc.56G>A p.Gly19Asp missense_variant Exon 1 of 5 NM_052965.4 ENSP00000493902.2 Q8WW01-1

Frequencies

GnomAD3 genomes
AF:
0.288
AC:
43806
AN:
151964
Hom.:
6956
Cov.:
32
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.:
35
AF XY:
0.340
AC XY:
232462
AN XY:
684630
show subpopulations
Gnomad4 AFR exome
AF:
0.139
AC:
4267
AN:
30742
Gnomad4 AMR exome
AF:
0.298
AC:
10532
AN:
35372
Gnomad4 ASJ exome
AF:
0.222
AC:
5548
AN:
24936
Gnomad4 EAS exome
AF:
0.452
AC:
15802
AN:
34966
Gnomad4 SAS exome
AF:
0.333
AC:
25964
AN:
78014
Gnomad4 FIN exome
AF:
0.412
AC:
18582
AN:
45090
Gnomad4 NFE exome
AF:
0.345
AC:
370619
AN:
1075266
Gnomad4 Remaining exome
AF:
0.326
AC:
18780
AN:
57618
Heterozygous variant carriers
0
16901
33802
50703
67604
84505
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
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.:
32
AF XY:
0.292
AC XY:
21726
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.152
AC:
0.151781
AN:
0.151781
Gnomad4 AMR
AF:
0.280
AC:
0.280081
AN:
0.280081
Gnomad4 ASJ
AF:
0.219
AC:
0.21902
AN:
0.21902
Gnomad4 EAS
AF:
0.472
AC:
0.47232
AN:
0.47232
Gnomad4 SAS
AF:
0.338
AC:
0.337894
AN:
0.337894
Gnomad4 FIN
AF:
0.414
AC:
0.414429
AN:
0.414429
Gnomad4 NFE
AF:
0.341
AC:
0.3406
AN:
0.3406
Gnomad4 OTH
AF:
0.281
AC:
0.281043
AN:
0.281043
Heterozygous variant carriers
0
1540
3079
4619
6158
7698
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
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
-
Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0093
T;.;.;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.026
N
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
T
MutationAssessor
Benign
1.9
L;L;.;.;.;.;.
PrimateAI
Uncertain
0.71
T
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
T
GERP RS
-1.6
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)

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

LitVar

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

Other links and lift over

dbSNP: rs2274432; hg19: chr1-184020945; COSMIC: COSV62294595; COSMIC: COSV62294595; API