3-12516442-A-ATGTG

Position:

• chr3-12516442-A-ATGTG

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_910-167insGTGT 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 0.047 (89 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-ATGTG is Benign according to our data. Variant chr3-12516442-A-ATGTG is described in ClinVar as [Likely_benign]. Clinvar id is 1217954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 4224 AN: 89016 Hom.: 89 Cov.: 0

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00840

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00107

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0824

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0474 AC: 4224 AN: 89094 Hom.: 89 Cov.: 0 AF XY: 0.0454 AC XY: 1942 AN XY: 42772

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00107

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.0435

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.0520

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

- -

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;