NM_025265.4:c.910-173delC

Variant names:

• chr3-12516437-AC-A
• rs376667792
• NM_025265.4:c.910-173delC

Variant summary

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

The NM_025265.4(TSEN2):​c.910-173delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 126,894 control chromosomes in the GnomAD database, including 590 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.093 (590 hom., cov: 26)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.92
• 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-AC-A is Benign according to our data. Variant chr3-12516437-AC-A is described in ClinVar as Benign. ClinVar VariationId is 1174286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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.910-173delC		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-173delC		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-173delC		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.910-173delC		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-173delC		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-173delC		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 11778 AN: 126788 Hom.: 590 Cov.: 26

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0558

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.0928 AC: 11775 AN: 126894 Hom.: 590 Cov.: 26 AF XY: 0.0940 AC XY: 5699 AN XY: 60652

African (AFR) AF: 0.0281 AC: 877 AN: 31158

American (AMR) AF: 0.126 AC: 1516 AN: 12046

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 317 AN: 3142

East Asian (EAS) AF: 0.0482 AC: 209 AN: 4334

South Asian (SAS) AF: 0.0501 AC: 177 AN: 3536

European-Finnish (FIN) AF: 0.134 AC: 1116 AN: 8320

Middle Eastern (MID) AF: 0.133 AC: 34 AN: 256

European-Non Finnish (NFE) AF: 0.118 AC: 7281 AN: 61562

Other (OTH) AF: 0.117 AC: 203 AN: 1734

Alfa AF: 0.0202 Hom.: 18

ClinVar

ClinVar submissions

Significance: 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		-2.9
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs376667792; hg19: chr3-12557936;