rs78685815

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000284995.11(TSEN2):​c.162G>A​(p.Ala54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,613,972 control chromosomes in the GnomAD database, including 1,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.065 ( 702 hom., cov: 32)
Exomes 𝑓: 0.022 ( 1037 hom. )

Consequence

TSEN2
ENST00000284995.11 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.64
Variant links:
Genes affected
TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 3-12489962-G-A is Benign according to our data. Variant chr3-12489962-G-A is described in ClinVar as [Benign]. Clinvar id is 137753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.64 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSEN2NM_025265.4 linkuse as main transcriptc.162G>A p.Ala54= synonymous_variant 2/12 ENST00000284995.11 NP_079541.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSEN2ENST00000284995.11 linkuse as main transcriptc.162G>A p.Ala54= synonymous_variant 2/121 NM_025265.4 ENSP00000284995 P2Q8NCE0-1

Frequencies

GnomAD3 genomes
AF:
0.0647
AC:
9842
AN:
152120
Hom.:
698
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.169
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.0694
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.0371
Gnomad SAS
AF:
0.0605
Gnomad FIN
AF:
0.0107
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0148
Gnomad OTH
AF:
0.0723
GnomAD3 exomes
AF:
0.0354
AC:
8910
AN:
251370
Hom.:
390
AF XY:
0.0329
AC XY:
4475
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.171
Gnomad AMR exome
AF:
0.0446
Gnomad ASJ exome
AF:
0.00407
Gnomad EAS exome
AF:
0.0338
Gnomad SAS exome
AF:
0.0580
Gnomad FIN exome
AF:
0.00971
Gnomad NFE exome
AF:
0.0152
Gnomad OTH exome
AF:
0.0324
GnomAD4 exome
AF:
0.0221
AC:
32341
AN:
1461734
Hom.:
1037
Cov.:
32
AF XY:
0.0221
AC XY:
16090
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.174
Gnomad4 AMR exome
AF:
0.0488
Gnomad4 ASJ exome
AF:
0.00375
Gnomad4 EAS exome
AF:
0.0437
Gnomad4 SAS exome
AF:
0.0558
Gnomad4 FIN exome
AF:
0.0102
Gnomad4 NFE exome
AF:
0.0136
Gnomad4 OTH exome
AF:
0.0314
GnomAD4 genome
AF:
0.0648
AC:
9859
AN:
152238
Hom.:
702
Cov.:
32
AF XY:
0.0646
AC XY:
4806
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.169
Gnomad4 AMR
AF:
0.0694
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.0373
Gnomad4 SAS
AF:
0.0597
Gnomad4 FIN
AF:
0.0107
Gnomad4 NFE
AF:
0.0148
Gnomad4 OTH
AF:
0.0758
Alfa
AF:
0.0310
Hom.:
133
Bravo
AF:
0.0727
Asia WGS
AF:
0.122
AC:
424
AN:
3478
EpiCase
AF:
0.0157
EpiControl
AF:
0.0172

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 04, 2014This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pontoneocerebellar hypoplasia Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.52
DANN
Benign
0.67
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs78685815; hg19: chr3-12531461; COSMIC: COSV53191301; API