chr3-12489962-G-C

Variant names:

• chr3-12489962-G-C
• rs78685815
• NM_025265.4:c.162G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_025265.4(TSEN2):​c.162G>C​(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSEN2 NM_025265.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.64
• Publications: 9 publications found

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]

TSEN2 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2B

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-12489962-G-C is Benign according to our data. Variant chr3-12489962-G-C is described in ClinVar as Benign. ClinVar VariationId is 160109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.64 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	NM_025265.4	MANE Select	c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 12	NP_079541.1
	TSEN2	NM_001321278.2		c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 12	NP_001308207.1
	TSEN2	NM_001145392.2		c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 12	NP_001138864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	ENST00000284995.11	TSL:1 MANE Select	c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 12	ENSP00000284995.6
	TSEN2	ENST00000402228.7	TSL:1	c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 12	ENSP00000385976.3
	TSEN2	ENST00000454502.6	TSL:1	c.162G>C	p.Ala54Ala	synonymous	Exon 2 of 13	ENSP00000392029.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.15
DANN	Benign	0.55
PhyloP100		-3.6
PromoterAI		0.0011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs78685815; hg19: chr3-12531461;