Variant 3-12516446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025265.4(TSEN2):c.910-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 126,484 control chromosomes in the GnomAD database, including 2,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2144 hom., cov: 21)

Consequence

TSEN2
NM_025265.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.431

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:

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

MKRN2OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 3-12516446-A-G is Benign according to our data. Variant chr3-12516446-A-G is described in ClinVar as [Benign]. Clinvar id is 1249008.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4 linkuse as main transcript	c.910-165A>G		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11 linkuse as main transcript	c.910-165A>G		intron_variant		1	NM_025265.4	P2	Q8NCE0-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

21220

AN:

126396

Hom.:

2136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.0162

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0753

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.168

AC:

21246

AN:

126484

Hom.:

2144

Cov.:

AF XY:

0.161

AC XY:

9895

AN XY:

61408

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.0417

Gnomad4 FIN

AF:

0.0753

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.4

DANN

Benign

0.16

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