rs10510421

Positions:

• chr3-12485743-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025265.4(TSEN2):​c.-18+863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,238 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (672 hom., cov: 32)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.-18+863C>T		intron_variant		ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11	c.-18+863C>T		intron_variant		1	NM_025265.4	ENSP00000284995	P2

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9679 AN: 152120 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0637 AC: 9693 AN: 152238 Hom.: 672 Cov.: 32 AF XY: 0.0635 AC XY: 4725 AN XY: 74452

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0681

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0419 Hom.: 50

Bravo AF: 0.0717

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.60

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: rs10510421; hg19: chr3-12527242;