chr19-54191203-G-T

Position:

• chr19-54191203-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000302937.8(TSEN34):​c.-4-158G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,384,726 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (53 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (369 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.88

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-54191203-G-T is Benign according to our data. Variant chr19-54191203-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	NM_001282332.2	c.-4-158G>T		intron_variant
TSEN34	NM_001282333.2	c.-4-158G>T		intron_variant
TSEN34	NM_001386740.1	c.-4-158G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000302937.8	c.-4-158G>T		intron_variant		1		P2
TSEN34	ENST00000396383.5	c.-4-158G>T		intron_variant		1		P2
TSEN34	ENST00000429671.7	c.-4-158G>T		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1973 AN: 151780 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00565 AC: 6971 AN: 1232826 Hom.: 369 Cov.: 33 AF XY: 0.00556 AC XY: 3327 AN XY: 597898

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.00324

Gnomad4 FIN exome AF: 0.0278

Gnomad4 NFE exome AF: 0.000352

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0131 AC: 1983 AN: 151900 Hom.: 53 Cov.: 33 AF XY: 0.0148 AC XY: 1096 AN XY: 74246

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.00852

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00343 Hom.: 2

Bravo AF: 0.0135

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 11, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.79

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: rs58123079; hg19: chr19-54695054;