3-12516464-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_025265.4(TSEN2):c.910-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 686,162 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (42 hom., cov: 30)
  • Exomes 𝑓: 0.016 (258 hom.)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 3-12516464-G-A is Benign according to our data. Variant chr3-12516464-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1187150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0154 (2335/151698) while in subpopulation AMR AF= 0.0439 (668/15208). AF 95% confidence interval is 0.0412. There are 42 homozygotes in gnomad4. There are 1220 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.910-147G>A		intron_variant		ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-147G>A		intron_variant		1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2328 AN: 151580 Hom.: 40 Cov.: 30

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0293

GnomAD4 exome AF: 0.0162 AC: 8638 AN: 534464 Hom.: 258 AF XY: 0.0162 AC XY: 4668 AN XY: 288136

Gnomad4 AFR exome AF: 0.00438

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.00326

Gnomad4 EAS exome AF: 0.0430

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.00989

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0154 AC: 2335 AN: 151698 Hom.: 42 Cov.: 30 AF XY: 0.0164 AC XY: 1220 AN XY: 74168

Gnomad4 AFR AF: 0.00573

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.0372

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0328

Alfa AF: 0.00175 Hom.: 1

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 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.067
Dann	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs761654828; hg19: chr3-12557963;