ENST00000302937:c.-175C>G

Variant names:

• chr19-54190280-C-G
• rs886054622
• ENST00000302937:c.-175C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000302937(TSEN34):​c.-175C>G variant causes a 5 prime UTR 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: 34)
• Consequence: TSEN34 ENST00000302937 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

Genes affected

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34	XM_011527294.4	c.-5+118C>G		intron_variant	Intron 1 of 4		XP_011525596.1
TSEN34	XM_047439391.1	c.-5+684C>G		intron_variant	Intron 1 of 4		XP_047295347.1
TSEN34	NM_001282333.2	c.-96C>G		upstream_gene_variant			NP_001269262.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000302937	c.-175C>G		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000305524.4
TSEN34	ENST00000429671	c.-96C>G		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000397402.4
TSEN34	ENST00000455798.6	c.-5+118C>G		intron_variant	Intron 1 of 4	2		ENSP00000400743.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 15

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.42

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: rs886054622; hg19: chr19-54694131;