NM_025265.4:c.910-128_910-123delTGTGTG

Variant names:

• chr3-12516446-ATGTGTG-A
• rs68107346
• NM_025265.4:c.910-128_910-123delTGTGTG

Variant summary

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

The NM_025265.4(TSEN2):​c.910-128_910-123delTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (91 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221
• 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-ATGTGTG-A is Benign according to our data. Variant chr3-12516446-ATGTGTG-A is described in ClinVar as Benign. ClinVar VariationId is 1295778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 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.910-128_910-123delTGTGTG		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-128_910-123delTGTGTG		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-128_910-123delTGTGTG		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_910-159delTGTGTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-164_910-159delTGTGTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-164_733-159delTGTGTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 4244 AN: 126276 Hom.: 91 Cov.: 0

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0444

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0288

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

GnomAD4 genome AF: 0.0337 AC: 4258 AN: 126366 Hom.: 91 Cov.: 0 AF XY: 0.0343 AC XY: 2106 AN XY: 61340

African (AFR) AF: 0.0621 AC: 2043 AN: 32902

American (AMR) AF: 0.0266 AC: 356 AN: 13384

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 53 AN: 2908

East Asian (EAS) AF: 0.0340 AC: 163 AN: 4800

South Asian (SAS) AF: 0.0550 AC: 237 AN: 4308

European-Finnish (FIN) AF: 0.0105 AC: 83 AN: 7930

Middle Eastern (MID) AF: 0.0313 AC: 8 AN: 256

European-Non Finnish (NFE) AF: 0.0215 AC: 1234 AN: 57408

Other (OTH) AF: 0.0284 AC: 51 AN: 1794

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		-0.22
Mutation Taster		=100/0	polymorphism

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;