19-54191164-C-G

Position:

• chr19-54191164-C-G

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.-4-197C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,364,770 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (297 hom., cov: 33)
  • Exomes 𝑓: 0.013 (334 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.430

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=-0.72).
• BP6: Variant 19-54191164-C-G is Benign according to our data. Variant chr19-54191164-C-G is described in ClinVar as [Benign]. Clinvar id is 1246046.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	NM_001282332.2	c.-5+127C>G		intron_variant
TSEN34	NM_001282333.2	c.-4-197C>G		intron_variant
TSEN34	NM_001386740.1	c.-4-197C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000302937.8	c.-4-197C>G		intron_variant		1		P2
TSEN34	ENST00000396383.5	c.-5+127C>G		intron_variant		1		P2
TSEN34	ENST00000429671.7	c.-4-197C>G		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6861 AN: 151682 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00841

Gnomad OTH AF: 0.0366

GnomAD4 exome AF: 0.0128 AC: 15551 AN: 1212978 Hom.: 334 Cov.: 32 AF XY: 0.0127 AC XY: 7443 AN XY: 586782

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0515

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.0556

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.0438

Gnomad4 NFE exome AF: 0.00728

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0452 AC: 6866 AN: 151792 Hom.: 297 Cov.: 33 AF XY: 0.0457 AC XY: 3391 AN XY: 74192

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.0144

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.00842

Gnomad4 OTH AF: 0.0367

Alfa AF: 0.00453 Hom.: 1

Bravo AF: 0.0504

Asia WGS AF: 0.0290 AC: 103 AN: 3476

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	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.3
DANN	Benign	0.75

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: rs78510537; hg19: chr19-54695015;