3-12484507-G-A

Position:

• chr3-12484507-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025265.4(TSEN2):​c.-391G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,144 control chromosomes in the GnomAD database, including 778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (778 hom., cov: 33)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: TSEN2 NM_025265.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.173

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-12484507-G-A is Benign according to our data. Variant chr3-12484507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 369384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN2	NM_025265.4	c.-391G>A		5_prime_UTR_variant	1/12	ENST00000284995.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN2	ENST00000284995.11	c.-391G>A		5_prime_UTR_variant	1/12	1	NM_025265.4	P2

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13516 AN: 152016 Hom.: 776 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0732

GnomAD4 exome AF: 0.143 AC: 2 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0890 AC: 13543 AN: 152130 Hom.: 778 Cov.: 33 AF XY: 0.0893 AC XY: 6641 AN XY: 74380

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0731 Hom.: 545

Bravo AF: 0.101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pontoneocerebellar hypoplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3806662; hg19: chr3-12526006;