3-12516446-ATGTGTGTGTG-A

Variant names:

• chr3-12516446-ATGTGTGTGTG-A
• rs68107346
• NM_025265.4:c.910-132_910-123delTGTGTGTGTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025265.4(TSEN2):​c.910-132_910-123delTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (419 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.779
• 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 -10 ACMG points.

• BP6: Variant 3-12516446-ATGTGTGTGTG-A is Benign according to our data. Variant chr3-12516446-ATGTGTGTGTG-A is described in ClinVar as Benign. ClinVar VariationId is 1270043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 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.910-132_910-123delTGTGTGTGTG		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-132_910-123delTGTGTGTGTG		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-132_910-123delTGTGTGTGTG		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_910-155delTGTGTGTGTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-164_910-155delTGTGTGTGTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-164_733-155delTGTGTGTGTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 8684 AN: 126376 Hom.: 419 Cov.: 0

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0688 AC: 8695 AN: 126464 Hom.: 419 Cov.: 0 AF XY: 0.0697 AC XY: 4277 AN XY: 61390

African (AFR) AF: 0.0272 AC: 894 AN: 32924

American (AMR) AF: 0.167 AC: 2239 AN: 13404

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 120 AN: 2912

East Asian (EAS) AF: 0.0192 AC: 92 AN: 4804

South Asian (SAS) AF: 0.0345 AC: 149 AN: 4314

European-Finnish (FIN) AF: 0.0961 AC: 764 AN: 7948

Middle Eastern (MID) AF: 0.00391 AC: 1 AN: 256

European-Non Finnish (NFE) AF: 0.0737 AC: 4234 AN: 57432

Other (OTH) AF: 0.0619 AC: 111 AN: 1792

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs68107346; hg19: chr3-12557945;