3-12516441-AATAT-A

Variant summary

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

The NM_025265.4(TSEN2):c.910-167_910-164del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.096 (189 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.779

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 3-12516441-AATAT-A is Benign according to our data. Variant chr3-12516441-AATAT-A is described in ClinVar as [Benign]. Clinvar id is 1236640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-167_910-164del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-167_910-164del		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 5345 AN: 55832 Hom.: 188 Cov.: 0

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.00503

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0692

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0958 AC: 5357 AN: 55930 Hom.: 189 Cov.: 0 AF XY: 0.0949 AC XY: 2539 AN XY: 26760

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.0485

Gnomad4 EAS AF: 0.00503

Gnomad4 SAS AF: 0.0401

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.103

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

Jul 13, 2018

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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: rs147950857; hg19: chr3-12557940;