3-12484797-TGCA-T

Position:

• chr3-12484797-TGCA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_025265.4(TSEN2):​c.-98_-96delAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 152,376 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (5 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: TSEN2 NM_025265.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.248

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-12484797-TGCA-T is Benign according to our data. Variant chr3-12484797-TGCA-T is described in ClinVar as [Benign]. Clinvar id is 2653539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00799 (1216/152166) while in subpopulation NFE AF= 0.0133 (904/67990). AF 95% confidence interval is 0.0126. There are 5 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.-98_-96delAGC		5_prime_UTR_variant	1/12	ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995	c.-98_-96delAGC		5_prime_UTR_variant	1/12	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1220 AN: 152048 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.0143 AC: 3 AN: 210 Hom.: 0 AF XY: 0.0179 AC XY: 3 AN XY: 168

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00799 AC: 1216 AN: 152166 Hom.: 5 Cov.: 33 AF XY: 0.00734 AC XY: 546 AN XY: 74412

Gnomad4 AFR AF: 0.00246

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00886 Hom.: 0

Bravo AF: 0.00803

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

TSEN2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs540848445; hg19: chr3-12526296;