3-12516446-ATGTG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025265.4(TSEN2):c.910-126_910-123del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (8278 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-12516446-ATGTG-A is Benign according to our data. Variant chr3-12516446-ATGTG-A is described in ClinVar as [Benign]. Clinvar id is 1295777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-126_910-123del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-126_910-123del		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 44615 AN: 125576 Hom.: 8280 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.355 AC: 44622 AN: 125662 Hom.: 8278 Cov.: 0 AF XY: 0.360 AC XY: 21949 AN XY: 60974

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.366

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs68107346; hg19: chr3-12557945;