1-184051999-C-G

Variant names:

• chr1-184051999-C-G
• rs58073693
• NM_052965.4:c.135+109C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052965.4(TSEN15):​c.135+109C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSEN15 NM_052965.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 1 publications found

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

TSEN15 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 2F

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052965.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	NM_052965.4	MANE Select	c.135+109C>G		intron	N/A	NP_443197.1	Q8WW01-1
	TSEN15	NM_001300764.2		c.135+109C>G		intron	N/A	NP_001287693.1	A0A2U3TZM3
	TSEN15	NM_001363643.2		c.135+109C>G		intron	N/A	NP_001350572.1	A0A2R8YDU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	ENST00000645668.2	MANE Select	c.135+109C>G		intron	N/A	ENSP00000493902.2	Q8WW01-1
	TSEN15	ENST00000361641.6	TSL:1	c.135+109C>G		intron	N/A	ENSP00000355299.2	A0A2U3TZM3
	TSEN15	ENST00000462677.3	TSL:1	n.135+109C>G		intron	N/A	ENSP00000432397.2	H0YCV5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		-0.29
PromoterAI		0.024	Neutral

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: rs58073693; hg19: chr1-184021133;