chr19-54190237-C-T

Position:

• chr19-54190237-C-T

Variant summary

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

The ENST00000455798.6(TSEN34):​c.-5+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 881,616 control chromosomes in the GnomAD database, including 681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (298 hom., cov: 34)
  • Exomes 𝑓: 0.019 (383 hom.)
• Consequence: TSEN34 ENST00000455798.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

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=-0.74).
• BP6: Variant 19-54190237-C-T is Benign according to our data. Variant chr19-54190237-C-T is described in ClinVar as [Benign]. Clinvar id is 1236557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	XM_011527294.4	c.-5+75C>T		intron_variant
TSEN34	XM_047439391.1	c.-5+641C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000455798.6	c.-5+75C>T		intron_variant		2		P2
TSEN34	ENST00000302937.8			upstream_gene_variant		1		P2
TSEN34	ENST00000429671.7			upstream_gene_variant		2		P2
TSEN34	ENST00000667261.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6868 AN: 151872 Hom.: 299 Cov.: 34

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.00839

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0187 AC: 13622 AN: 729624 Hom.: 383 Cov.: 10 AF XY: 0.0177 AC XY: 6694 AN XY: 377982

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0675

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0569

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0458

Gnomad4 NFE exome AF: 0.00793

Gnomad4 OTH exome AF: 0.0238

GnomAD4 genome AF: 0.0452 AC: 6873 AN: 151992 Hom.: 298 Cov.: 34 AF XY: 0.0457 AC XY: 3392 AN XY: 74300

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0540

Gnomad4 SAS AF: 0.0142

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.00839

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.00917 Hom.: 3

Bravo AF: 0.0503

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	Feb 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.78
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75899395; hg19: chr19-54694088; COSMIC: COSV55475491;