3-12492254-TA-T

Variant names:

• chr3-12492254-TA-T
• rs144898008
• NM_025265.4:c.271+39delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025265.4(TSEN2):​c.271+39delA 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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2B

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	NM_025265.4	MANE Select	c.271+39delA		intron	N/A	NP_079541.1
	TSEN2	NM_001321278.2		c.271+39delA		intron	N/A	NP_001308207.1
	TSEN2	NM_001145392.2		c.271+39delA		intron	N/A	NP_001138864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	ENST00000284995.11	TSL:1 MANE Select	c.271+38delA		intron	N/A	ENSP00000284995.6
	TSEN2	ENST00000402228.7	TSL:1	c.271+38delA		intron	N/A	ENSP00000385976.3
	TSEN2	ENST00000454502.6	TSL:1	c.271+38delA		intron	N/A	ENSP00000392029.2

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

GnomAD2 exomes AF: 0.0244 AC: 6123 AN: 250718 AF XY: 0.0248

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 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

African (AFR) AF: 0.0311 AC: 999 AN: 32132

American (AMR) AF: 0.0386 AC: 1724 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 89 AN: 25746

East Asian (EAS) AF: 0.0434 AC: 1707 AN: 39342

South Asian (SAS) AF: 0.0552 AC: 4684 AN: 84868

European-Finnish (FIN) AF: 0.0102 AC: 543 AN: 53182

Middle Eastern (MID) AF: 0.0134 AC: 71 AN: 5296

European-Non Finnish (NFE) AF: 0.0126 AC: 13284 AN: 1052988

Other (OTH) AF: 0.0196 AC: 1136 AN: 58016

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

African (AFR) AF: 0.0334 AC: 1389 AN: 41574

American (AMR) AF: 0.0470 AC: 719 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.0377 AC: 196 AN: 5194

South Asian (SAS) AF: 0.0596 AC: 288 AN: 4832

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 921 AN: 68028

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

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

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs144898008; hg19: chr3-12533753;