ENST00000396383.5:c.-121G>T

Variant names:

• chr19-54190921-G-T
• rs145947907
• ENST00000396383.5:c.-121G>T

Variant summary

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

The ENST00000396383.5(TSEN34):​c.-121G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,050,114 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: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: TSEN34 ENST00000396383.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• 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=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396383.5. 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_001282332.2		c.-121G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001269261.1	Q9BSV6
	TSEN34	NM_001282332.2		c.-121G>T		5_prime_UTR	Exon 1 of 5	NP_001269261.1	Q9BSV6
	TSEN34	NM_001282333.2		c.-4-440G>T		intron	N/A	NP_001269262.2	A0A590UJW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN34	ENST00000396383.5	TSL:1	c.-121G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000379667.1	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.-121G>T		5_prime_UTR	Exon 1 of 5	ENSP00000379667.1	Q9BSV6
	TSEN34	ENST00000302937.8	TSL:1	c.-4-440G>T		intron	N/A	ENSP00000305524.4	Q9BSV6

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152260 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 18 AN: 897736 Hom.: 0 Cov.: 31 AF XY: 0.0000383 AC XY: 16 AN XY: 417386

African (AFR) AF: 0.00 AC: 0 AN: 17466

American (AMR) AF: 0.00 AC: 0 AN: 2766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7200

East Asian (EAS) AF: 0.000146 AC: 1 AN: 6830

South Asian (SAS) AF: 0.00 AC: 0 AN: 21966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1930

European-Non Finnish (NFE) AF: 0.0000211 AC: 17 AN: 804440

Other (OTH) AF: 0.00 AC: 0 AN: 31418

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152378 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41602

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		0.92
PromoterAI		-0.043	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: rs145947907; hg19: chr19-54694772;