3-12516444-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.792

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 -14 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 id is 1235965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-167A>G		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-167A>G		intron_variant		1	NM_025265.4	P2

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

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.00784

Gnomad4 SAS AF: 0.0982

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.264

Alfa AF: 0.0111 Hom.: 0

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 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.7
Dann	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs1699352; hg19: chr3-12557943; COSMIC: COSV53190480; COSMIC: COSV53190480;