3-12516446-ATGTGTGTGTGTGTGTGTGTGTGTGTG-ATGTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr3-12516446-ATG-A
• rs68107346
• NM_025265.4:c.910-124_910-123delTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_025265.4(TSEN2):​c.910-124_910-123delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.026 (70 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

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]

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-124_910-123delTG		intron_variant	Intron 6 of 11	ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-164_910-163delTG		intron_variant	Intron 6 of 11	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3302 AN: 126374 Hom.: 71 Cov.: 0

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0162

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.00980

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0261 AC: 3305 AN: 126462 Hom.: 70 Cov.: 0 AF XY: 0.0274 AC XY: 1683 AN XY: 61406

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0532

Gnomad4 FIN AF: 0.00980

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs68107346; hg19: chr3-12557945;