3-12516437-ACAAAATAT-A

Variant summary

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

The NM_025265.4(TSEN2):c.910-173_910-166del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.063 (285 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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-ACAAAATAT-A is Benign according to our data. Variant chr3-12516437-ACAAAATAT-A is described in ClinVar as [Benign]. Clinvar id is 1296237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-173_910-166del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-173_910-166del		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 8011 AN: 126590 Hom.: 285 Cov.: 0

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0981

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.0511

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0634

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

GnomAD4 genome AF: 0.0632 AC: 8013 AN: 126696 Hom.: 285 Cov.: 0 AF XY: 0.0630 AC XY: 3813 AN XY: 60550

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0558

Gnomad4 ASJ AF: 0.0981

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0862

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.0632

Alfa AF: 0.116 Hom.: 112

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 07, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140042646; hg19: chr3-12557936;