rs144898008

Positions:

• chr3-12492254-TA-T
• chr3-12492254-TA-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025265.4(TSEN2):​c.271+39del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,548,512 control chromosomes in the GnomAD database, including 492 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (66 hom., cov: 33)
  • Exomes 𝑓: 0.017 (426 hom.)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-12492254-TA-T is Benign according to our data. Variant chr3-12492254-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 261877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.271+39del		intron_variant		ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11	c.271+39del		intron_variant		1	NM_025265.4	ENSP00000284995	P2

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3718 AN: 152208 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0244 AC: 6123 AN: 250718 Hom.: 131 AF XY: 0.0248 AC XY: 3364 AN XY: 135576

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.0338

Gnomad SAS exome AF: 0.0575

Gnomad FIN exome AF: 0.00972

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0174 AC: 24237 AN: 1396190 Hom.: 426 Cov.: 21 AF XY: 0.0181 AC XY: 12640 AN XY: 698700

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.0386

Gnomad4 ASJ exome AF: 0.00346

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.0552

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0196

GnomAD4 genome AF: 0.0245 AC: 3728 AN: 152322 Hom.: 66 Cov.: 33 AF XY: 0.0260 AC XY: 1934 AN XY: 74498

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0146 Hom.: 2

Bravo AF: 0.0258

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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: rs144898008; hg19: chr3-12533753;