3-12516446-A-ATGTGTGTGTG

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_025265.4(TSEN2):​c.910-132_910-123dupTGTGTGTGTG 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 0.000055 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000553 (7/126556) while in subpopulation EAS AF = 0.00125 (6/4804). AF 95% confidence interval is 0.000543. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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_910-123dupTGTGTGTGTG		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-132_910-123dupTGTGTGTGTG		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-132_910-123dupTGTGTGTGTG		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.910-165_910-164insTGTGTGTGTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-165_910-164insTGTGTGTGTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-165_733-164insTGTGTGTGTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.0000553 AC: 7 AN: 126468 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00125

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000553 AC: 7 AN: 126556 Hom.: 0 Cov.: 0 AF XY: 0.0000814 AC XY: 5 AN XY: 61446

African (AFR) AF: 0.0000304 AC: 1 AN: 32930

American (AMR) AF: 0.00 AC: 0 AN: 13420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2912

East Asian (EAS) AF: 0.00125 AC: 6 AN: 4804

South Asian (SAS) AF: 0.00 AC: 0 AN: 4316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57480

Other (OTH) AF: 0.00 AC: 0 AN: 1794

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

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;