NM_025265.4:c.910-167A>G

Variant names:

• chr3-12516444-A-G
• rs1699352
• NM_025265.4:c.910-167A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025265.4(TSEN2):​c.910-167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.24 (612 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.792
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-12516444-A-G is Benign according to our data. Variant chr3-12516444-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 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.910-167A>G		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.910-167A>G		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.910-167A>G		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.910-167A>G		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.910-167A>G		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.733-167A>G		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 12256 AN: 51422 Hom.: 610 Cov.: 0

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0539

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.00785

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.238 AC: 12263 AN: 51488 Hom.: 612 Cov.: 0 AF XY: 0.234 AC XY: 5681 AN XY: 24242

African (AFR) AF: 0.278 AC: 3204 AN: 11530

American (AMR) AF: 0.238 AC: 1098 AN: 4608

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 443 AN: 1470

East Asian (EAS) AF: 0.00784 AC: 18 AN: 2296

South Asian (SAS) AF: 0.0982 AC: 154 AN: 1568

European-Finnish (FIN) AF: 0.193 AC: 564 AN: 2926

Middle Eastern (MID) AF: 0.142 AC: 17 AN: 120

European-Non Finnish (NFE) AF: 0.252 AC: 6579 AN: 26104

Other (OTH) AF: 0.264 AC: 175 AN: 662

Alfa AF: 0.0111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.30
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1699352; hg19: chr3-12557943; COSMIC: COSV53190480; COSMIC: COSV53190480;