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. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	NM_025265.4	MANE Select	c.910-124_910-123delTG		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-124_910-123delTG		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-124_910-123delTG		intron	N/A	NP_001138864.1	Q8NCE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	ENST00000284995.11	TSL:1 MANE Select	c.910-164_910-163delTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-164_910-163delTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-164_733-163delTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

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

African (AFR) AF: 0.0145 AC: 477 AN: 32914

American (AMR) AF: 0.0329 AC: 441 AN: 13408

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 154 AN: 2908

East Asian (EAS) AF: 0.115 AC: 551 AN: 4798

South Asian (SAS) AF: 0.0532 AC: 229 AN: 4304

European-Finnish (FIN) AF: 0.00980 AC: 78 AN: 7960

Middle Eastern (MID) AF: 0.0977 AC: 25 AN: 256

European-Non Finnish (NFE) AF: 0.0224 AC: 1284 AN: 57444

Other (OTH) AF: 0.0307 AC: 55 AN: 1792

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs68107346;

hg19: chr3-12557945;