ENST00000302937.8:c.-4-158G>A

Variant names:

• chr19-54191203-G-A
• rs58123079
• ENST00000302937.8:c.-4-158G>A

Variant summary

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

The ENST00000302937.8(TSEN34):​c.-4-158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,232,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

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]

TSEN34 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2C

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: ENST00000302937.8. 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
	TSEN34	NM_001282333.2		c.-4-158G>A		intron	N/A	NP_001269262.2	A0A590UJW4
	TSEN34	NM_001282332.2		c.-4-158G>A		intron	N/A	NP_001269261.1	Q9BSV6
	TSEN34	NM_001386740.1		c.-4-158G>A		intron	N/A	NP_001373669.1	Q9BSV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN34	ENST00000302937.8	TSL:1	c.-4-158G>A		intron	N/A	ENSP00000305524.4	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.-4-158G>A		intron	N/A	ENSP00000379667.1	Q9BSV6
	TSEN34	ENST00000667261.1		c.-4-158G>A		intron	N/A	ENSP00000499595.1	A0A590UJW4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000105 AC: 13 AN: 1232842 Hom.: 0 Cov.: 33 AF XY: 0.0000100 AC XY: 6 AN XY: 597904

African (AFR) AF: 0.00 AC: 0 AN: 23430

American (AMR) AF: 0.00 AC: 0 AN: 14014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16802

East Asian (EAS) AF: 0.00 AC: 0 AN: 29368

South Asian (SAS) AF: 0.00 AC: 0 AN: 55912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3424

European-Non Finnish (NFE) AF: 0.0000129 AC: 13 AN: 1007114

Other (OTH) AF: 0.00 AC: 0 AN: 50472

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.19
DANN	Benign	0.93
PhyloP100		-1.9
PromoterAI		-0.014	Neutral

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

Other links and lift over

dbSNP: rs58123079; hg19: chr19-54695054;