3-12516437-ACAAAAT-A

Position:

• chr3-12516437-ACAAAAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000284995.11(TSEN2):​c.910-173_910-168del 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 0.0085 (12 hom., cov: 0)
• Consequence: TSEN2 ENST00000284995.11 intron
• Clinical Significance: Likely 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-ACAAAAT-A is Benign according to our data. Variant chr3-12516437-ACAAAAT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00846 (1074/127024) while in subpopulation AMR AF= 0.0153 (185/12080). AF 95% confidence interval is 0.0135. There are 12 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-173_910-168del		intron_variant		ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-173_910-168del		intron_variant		1	NM_025265.4	ENSP00000284995	P2

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1073 AN: 126918 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.000318

Gnomad EAS AF: 0.00737

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00935

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

GnomAD4 genome AF: 0.00846 AC: 1074 AN: 127024 Hom.: 12 Cov.: 0 AF XY: 0.00868 AC XY: 527 AN XY: 60714

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.000318

Gnomad4 EAS AF: 0.00738

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00360

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00923

Alfa AF: 0.00895 Hom.: 0

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

Sep 22, 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: rs1365099363; hg19: chr3-12557936;