3-12516442-A-ATG

Variant summary

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

The NM_025265.4(TSEN2):c.910-168_910-167insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.034 (52 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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 3-12516442-A-ATG is Benign according to our data. Variant chr3-12516442-A-ATG is described in ClinVar as [Likely_benign]. Clinvar id is 1202067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-168_910-167insGT		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-168_910-167insGT		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 3025 AN: 89056 Hom.: 51 Cov.: 0

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000712

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0110

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0340 AC: 3031 AN: 89134 Hom.: 52 Cov.: 0 AF XY: 0.0339 AC XY: 1449 AN XY: 42792

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000712

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0419

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 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: rs1491196550; hg19: chr3-12557941;