3-12516437-AC-A

Position:

• chr3-12516437-AC-A

Variant summary

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

The NM_025265.4(TSEN2):​c.910-173del 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

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 3-12516437-AC-A is Benign according to our data. Variant chr3-12516437-AC-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-173del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-173del		intron_variant		1	NM_025265.4	P2

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

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0202 Hom.: 18

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

Jun 28, 2018

- -

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: rs376667792; hg19: chr3-12557936;