3-12516442-A-ATGTGTGTG

Variant names:

• chr3-12516442-A-ATGTGTGTG
• rs1491196550
• NM_025265.4:c.910-168_910-167insGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_025265.4(TSEN2):​c.910-168_910-167insGTGTGTGT 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 0.0057 (3 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 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.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00568 (506/89156) while in subpopulation NFE AF = 0.00848 (354/41766). AF 95% confidence interval is 0.00775. There are 3 homozygotes in GnomAd4. There are 230 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.910-168_910-167insGTGTGTGT		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-168_910-167insGTGTGTGT		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-168_910-167insGTGTGTGT		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.910-169_910-168insTGTGTGTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-169_910-168insTGTGTGTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-169_733-168insTGTGTGTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.00568 AC: 506 AN: 89078 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.00702

Gnomad EAS AF: 0.000712

Gnomad SAS AF: 0.00276

Gnomad FIN AF: 0.00317

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00847

Gnomad OTH AF: 0.00775

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

GnomAD4 genome AF: 0.00568 AC: 506 AN: 89156 Hom.: 3 Cov.: 0 AF XY: 0.00537 AC XY: 230 AN XY: 42812

African (AFR) AF: 0.00196 AC: 48 AN: 24512

American (AMR) AF: 0.00706 AC: 51 AN: 7220

Ashkenazi Jewish (ASJ) AF: 0.00702 AC: 16 AN: 2278

East Asian (EAS) AF: 0.000712 AC: 2 AN: 2808

South Asian (SAS) AF: 0.00277 AC: 7 AN: 2530

European-Finnish (FIN) AF: 0.00317 AC: 19 AN: 5990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.00848 AC: 354 AN: 41766

Other (OTH) AF: 0.00768 AC: 9 AN: 1172

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
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: rs1491196550; hg19: chr3-12557941;