chr3-12516442-A-ATGTG

Variant names:

• chr3-12516442-A-ATGTG
• rs1491196550
• NM_025265.4:c.910-168_910-167insGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025265.4(TSEN2):​c.910-168_910-167insGTGT 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 0.047 (89 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-12516442-A-ATGTG is Benign according to our data. Variant chr3-12516442-A-ATGTG is described in ClinVar as Likely_benign. ClinVar VariationId is 1217954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 4224 AN: 89016 Hom.: 89 Cov.: 0

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00840

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00107

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0824

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0474 AC: 4224 AN: 89094 Hom.: 89 Cov.: 0 AF XY: 0.0454 AC XY: 1942 AN XY: 42772

African (AFR) AF: 0.0221 AC: 542 AN: 24496

American (AMR) AF: 0.0465 AC: 335 AN: 7212

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 257 AN: 2276

East Asian (EAS) AF: 0.00107 AC: 3 AN: 2808

South Asian (SAS) AF: 0.0111 AC: 28 AN: 2530

European-Finnish (FIN) AF: 0.0435 AC: 260 AN: 5974

Middle Eastern (MID) AF: 0.0783 AC: 13 AN: 166

European-Non Finnish (NFE) AF: 0.0651 AC: 2719 AN: 41746

Other (OTH) AF: 0.0520 AC: 61 AN: 1172

Alfa AF: 0.00 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		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;