3-12516446-ATGTGTG-A

Variant summary

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

The NM_025265.4(TSEN2):c.910-128_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 0.034 (91 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-ATGTGTG-A is Benign according to our data. Variant chr3-12516446-ATGTGTG-A is described in ClinVar as [Benign]. Clinvar id is 1295778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-128_910-123del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-128_910-123del		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 4244 AN: 126276 Hom.: 91 Cov.: 0

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0444

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0288

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

GnomAD4 genome AF: 0.0337 AC: 4258 AN: 126366 Hom.: 91 Cov.: 0 AF XY: 0.0343 AC XY: 2106 AN XY: 61340

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0284

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 05, 2019

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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: rs68107346; hg19: chr3-12557945;