rs709160

chr3-12484903-G-Cchr3-12484903-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025265.4(TSEN2):c.-18+23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,124 control chromosomes in the GnomAD database, including 24,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (24461 hom., cov: 32)
  • Exomes 𝑓: 0.37 (3 hom.)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-12484903-G-C is Benign according to our data. Variant chr3-12484903-G-C is described in ClinVar as [Benign]. Clinvar id is 1273097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.-18+23G>C		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.-18+23G>C		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82938 AN: 151968 Hom.: 24432 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.538

GnomAD4 exome AF: 0.368 AC: 14 AN: 38 Hom.: 3 Cov.: 0 AF XY: 0.300 AC XY: 9 AN XY: 30

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.546 AC: 83009 AN: 152086 Hom.: 24461 Cov.: 32 AF XY: 0.538 AC XY: 40016 AN XY: 74312

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.537

Alfa AF: 0.515 Hom.: 2508

Bravo AF: 0.552

Asia WGS AF: 0.321 AC: 1117 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

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.66
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs709160; hg19: chr3-12526402;