3-12488685-G-T

Position:

• chr3-12488685-G-T

Variant summary

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

The NM_025265.4(TSEN2):​c.-17-1099G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,240 control chromosomes in the GnomAD database, including 696 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 0.065 (696 hom., cov: 32)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.-17-1099G>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.-17-1099G>T		intron_variant		1	NM_025265.4	ENSP00000284995	P2

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9813 AN: 152122 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0646 AC: 9828 AN: 152240 Hom.: 696 Cov.: 32 AF XY: 0.0645 AC XY: 4800 AN XY: 74442

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0740

Alfa AF: 0.00269 Hom.: 0

Bravo AF: 0.0726

Asia WGS AF: 0.100 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.56

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: rs3856808; hg19: chr3-12530184;