3-12516446-ATGTGTGTG-A

Variant summary

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

The NM_025265.4(TSEN2):c.910-130_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 0.046 (326 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 3-12516446-ATGTGTGTG-A is Benign according to our data. Variant chr3-12516446-ATGTGTGTG-A is described in ClinVar as [Benign]. Clinvar id is 1281198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-130_910-123del		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-130_910-123del		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 5835 AN: 126356 Hom.: 325 Cov.: 0

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00378

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.0328

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

GnomAD4 genome AF: 0.0462 AC: 5842 AN: 126444 Hom.: 326 Cov.: 0 AF XY: 0.0456 AC XY: 2797 AN XY: 61390

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.00378

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.0324

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 11, 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;