3-12516446-ATGTGTGTGTGTGTGTGTGTGTGTGTG-ATGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr3-12516446-A-ATG
• rs68107346
• NM_025265.4:c.910-124_910-123dupTG

Variant summary

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

The NM_025265.4(TSEN2):​c.910-124_910-123dupTG 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 0.0022 (1 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 sas. GnomAd4 allele frequency = 0.00224 (283/126546) while in subpopulation SAS AF = 0.00996 (43/4316). AF 95% confidence interval is 0.0076. There are 1 homozygotes in GnomAd4. There are 149 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.910-124_910-123dupTG		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-124_910-123dupTG		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-124_910-123dupTG		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_910-164insTG		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-165_910-164insTG		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-165_733-164insTG		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 283 AN: 126458 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00103

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.000957

Gnomad OTH AF: 0.00226

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

GnomAD4 genome AF: 0.00224 AC: 283 AN: 126546 Hom.: 1 Cov.: 0 AF XY: 0.00243 AC XY: 149 AN XY: 61440

African (AFR) AF: 0.00343 AC: 113 AN: 32922

American (AMR) AF: 0.00171 AC: 23 AN: 13420

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 3 AN: 2912

East Asian (EAS) AF: 0.00832 AC: 40 AN: 4806

South Asian (SAS) AF: 0.00996 AC: 43 AN: 4316

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

Middle Eastern (MID) AF: 0.00781 AC: 2 AN: 256

European-Non Finnish (NFE) AF: 0.000957 AC: 55 AN: 57476

Other (OTH) AF: 0.00223 AC: 4 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
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;