Genetic Variant TSEN2:c.910-138_910-123delTGTGTGTGTGTGTGTG (chr3-12516446-ATGTGTGTGTGTGTGTG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_025265.4(TSEN2):c.910-138_910-123delTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 41 hom., cov: 0)

Consequence

TSEN2
NM_025265.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.779

Publications

1 publications found

Variant links:

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]

TSEN2 links:

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

MKRN2OS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0187 (2366/126550) while in subpopulation AMR AF = 0.0496 (665/13416). AF 95% confidence interval is 0.0464. There are 41 homozygotes in GnomAd4. There are 1234 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSEN2	NM_025265.4	MANE Select	c.910-138_910-123delTGTGTGTGTGTGTGTG	intron	N/A	NP_079541.1	Q8NCE0-1
TSEN2	NM_001321278.2		c.910-138_910-123delTGTGTGTGTGTGTGTG	intron	N/A	NP_001308207.1	C9J7Z4
TSEN2	NM_001145392.2		c.910-138_910-123delTGTGTGTGTGTGTGTG	intron	N/A	NP_001138864.1	Q8NCE0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSEN2	ENST00000284995.11	TSL:1 MANE Select	c.910-164_910-149delTGTGTGTGTGTGTGTG	intron	N/A	ENSP00000284995.6	Q8NCE0-1
TSEN2	ENST00000402228.7	TSL:1	c.910-164_910-149delTGTGTGTGTGTGTGTG	intron	N/A	ENSP00000385976.3	Q8NCE0-1
TSEN2	ENST00000454502.6	TSL:1	c.733-164_733-149delTGTGTGTGTGTGTGTG	intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2361

AN:

126462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.00309

Gnomad EAS

AF:

0.0399

Gnomad SAS

AF:

0.0333

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0145

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.0339

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

GnomAD4 genome

AF:

0.0187

AC:

2366

AN:

126550

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

1234

AN XY:

61442

show subpopulations

African (AFR)

AF:

0.00820

AC:

270

AN:

32928

American (AMR)

AF:

0.0496

AC:

665

AN:

13416

Ashkenazi Jewish (ASJ)

AF:

0.00309

AC:

AN:

2912

East Asian (EAS)

AF:

0.0400

AC:

192

AN:

4806

South Asian (SAS)

AF:

0.0327

AC:

141

AN:

4316

European-Finnish (FIN)

AF:

0.0137

AC:

109

AN:

7964

Middle Eastern (MID)

AF:

0.0156

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.0158

AC:

908

AN:

57480

Other (OTH)

AF:

0.0379

AC:

AN:

1794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

188

281

375

469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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3-12516446-ATGTGTGTGTGTGTGTGTGTGTGTGTG-ATGTGTGTGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over