3-12516441-AATAT-AAT

Variant names:

• chr3-12516441-AAT-A
• rs147950857
• NM_025265.4:c.910-165_910-164delAT

Variant summary

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

The NM_025265.4(TSEN2):​c.910-165_910-164delAT 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 0.13 (602 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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 (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-165_910-164delAT		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.910-169_910-168delAT		intron_variant	Intron 6 of 11	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.132 AC: 7377 AN: 55846 Hom.: 598 Cov.: 0

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.000718

Gnomad SAS AF: 0.00691

Gnomad FIN AF: 0.00818

Gnomad MID AF: 0.0692

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.132 AC: 7394 AN: 55944 Hom.: 602 Cov.: 0 AF XY: 0.129 AC XY: 3442 AN XY: 26766

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0436

Gnomad4 EAS AF: 0.000718

Gnomad4 SAS AF: 0.00693

Gnomad4 FIN AF: 0.00818

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.128

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: rs147950857; hg19: chr3-12557940;