19-54190483-G-C

Position:

• chr19-54190483-G-C

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.-5+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,371,970 control chromosomes in the GnomAD database, including 37,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2982 hom., cov: 34)
  • Exomes 𝑓: 0.23 (34750 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.458

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=-0.78).
• BP6: Variant 19-54190483-G-C is Benign according to our data. Variant chr19-54190483-G-C is described in ClinVar as [Benign]. Clinvar id is 1250386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	NM_001282333.2	c.-5+112G>C		intron_variant
TSEN34	NM_001386740.1	c.-5+112G>C		intron_variant
TSEN34	NM_024075.5	c.-5+33G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000302937.8	c.-5+33G>C		intron_variant		1		P2
TSEN34	ENST00000429671.7	c.-5+112G>C		intron_variant		2		P2
TSEN34	ENST00000455798.6	c.-5+321G>C		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26377 AN: 151832 Hom.: 2983 Cov.: 34

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.234 AC: 285671 AN: 1220022 Hom.: 34750 Cov.: 26 AF XY: 0.233 AC XY: 137467 AN XY: 589352

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.0387

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.174 AC: 26383 AN: 151948 Hom.: 2982 Cov.: 34 AF XY: 0.173 AC XY: 12860 AN XY: 74260

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.177

Alfa AF: 0.108 Hom.: 187

Bravo AF: 0.165

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs16985457; hg19: chr19-54694334; COSMIC: COSV55475683; COSMIC: COSV55475683;