Variant 3-12516569-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025265.4(TSEN2):c.910-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,606,704 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 42 hom., cov: 31)

Exomes 𝑓: 0.015 ( 273 hom. )

Consequence

TSEN2
NM_025265.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.208

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-12516569-A-G is Benign according to our data. Variant chr3-12516569-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1214522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0178 (2702/151832) while in subpopulation AMR AF= 0.0457 (696/15226). AF 95% confidence interval is 0.0429. There are 42 homozygotes in gnomad4. There are 1396 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4 linkuse as main transcript	c.910-42A>G		intron_variant		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.910-42A>G		intron_variant		1	NM_025265.4	ENSP00000284995.6		Q8NCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2693

AN:

151714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0457

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.0380

Gnomad SAS

AF:

0.0301

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0327

GnomAD3 exomes

AF:

0.0195

AC:

4908

AN:

251124

Hom.:

AF XY:

0.0193

AC XY:

2619

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0340

Gnomad SAS exome

AF:

0.0306

Gnomad FIN exome

AF:

0.00972

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0152

AC:

22045

AN:

1454872

Hom.:

273

Cov.:

AF XY:

0.0152

AC XY:

11036

AN XY:

724212

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.00345

Gnomad4 EAS exome

AF:

0.0433

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0178

AC:

2702

AN:

151832

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1396

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.0457

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.0380

Gnomad4 SAS

AF:

0.0295

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.0366

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.81

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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