chr3-12516437-ACAAAAT-A

Variant names:

• chr3-12516437-ACAAAAT-A
• rs1365099363
• NM_025265.4:c.910-173_910-168delCAAAAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_025265.4(TSEN2):​c.910-173_910-168delCAAAAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0085 (12 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02
• 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 -10 ACMG points.

• BP6: Variant 3-12516437-ACAAAAT-A is Benign according to our data. Variant chr3-12516437-ACAAAAT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1212240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00846 (1074/127024) while in subpopulation AMR AF = 0.0153 (185/12080). AF 95% confidence interval is 0.0135. There are 12 homozygotes in GnomAd4. There are 527 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 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.910-173_910-168delCAAAAT		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-173_910-168delCAAAAT		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-173_910-168delCAAAAT		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.910-173_910-168delCAAAAT		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-173_910-168delCAAAAT		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-173_733-168delCAAAAT		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1073 AN: 126918 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.000318

Gnomad EAS AF: 0.00737

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00935

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

GnomAD4 genome AF: 0.00846 AC: 1074 AN: 127024 Hom.: 12 Cov.: 0 AF XY: 0.00868 AC XY: 527 AN XY: 60714

African (AFR) AF: 0.00327 AC: 102 AN: 31180

American (AMR) AF: 0.0153 AC: 185 AN: 12080

Ashkenazi Jewish (ASJ) AF: 0.000318 AC: 1 AN: 3144

East Asian (EAS) AF: 0.00738 AC: 32 AN: 4334

South Asian (SAS) AF: 0.00311 AC: 11 AN: 3536

European-Finnish (FIN) AF: 0.00360 AC: 30 AN: 8342

Middle Eastern (MID) AF: 0.0156 AC: 4 AN: 256

European-Non Finnish (NFE) AF: 0.0112 AC: 693 AN: 61610

Other (OTH) AF: 0.00923 AC: 16 AN: 1734

Alfa AF: 0.00895 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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		1.0
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: rs1365099363; hg19: chr3-12557936;