rs77899976

Positions:

chr3-12503280-G-A

Variant summary

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

The NM_025265.4(TSEN2):c.327G>A(p.Glu109Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,160 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 66 hom., cov: 32)

Exomes 𝑓: 0.017 ( 437 hom. )

Consequence

TSEN2
NM_025265.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.600

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]

TSEN2 links:

TSEN2 (HGNC:):

TSEN2 links:

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=-0.87).

BP6

Variant 3-12503280-G-A is Benign according to our data. Variant chr3-12503280-G-A is described in ClinVar as [Benign]. Clinvar id is 137749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4 linkuse as main transcript	c.327G>A	p.Glu109Glu	synonymous_variant	5/12	ENST00000284995.11	NP_079541.1	Q8NCE0-1A0A024R2G3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11 linkuse as main transcript	c.327G>A	p.Glu109Glu	synonymous_variant	5/12	1	NM_025265.4	ENSP00000284995.6		Q8NCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3728

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0245

AC:

6152

AN:

250798

Hom.:

132

AF XY:

0.0249

AC XY:

3380

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0316

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0338

Gnomad SAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.00970

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0175

AC:

25532

AN:

1461866

Hom.:

437

Cov.:

AF XY:

0.0182

AC XY:

13223

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.0436

Gnomad4 SAS exome

AF:

0.0554

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0245

AC:

3738

AN:

152294

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1943

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0472

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0378

Gnomad4 SAS

AF:

0.0594

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.0394

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0910

AC:

316

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0158

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 submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 04, 2014	This 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 submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pontoneocerebellar hypoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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

-0.87

CADD

Benign

0.14

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over