19-54191191-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000302937.8(TSEN34):c.-4-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,387,238 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (7 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 19-54191191-G-C is Benign according to our data. Variant chr19-54191191-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (970/152214) while in subpopulation AFR AF= 0.0213 (887/41552). AF 95% confidence interval is 0.0202. There are 16 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN34	NM_001282332.2	c.-5+154G>C		intron_variant
TSEN34	NM_001282333.2	c.-4-170G>C		intron_variant
TSEN34	NM_001386740.1	c.-4-170G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN34	ENST00000302937.8	c.-4-170G>C		intron_variant		1		P2
TSEN34	ENST00000396383.5	c.-5+154G>C		intron_variant		1		P2
TSEN34	ENST00000429671.7	c.-4-170G>C		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152098 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.000572 AC: 706 AN: 1235024 Hom.: 7 Cov.: 33 AF XY: 0.000558 AC XY: 334 AN XY: 599018

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.00169

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000396

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00637 AC: 970 AN: 152214 Hom.: 16 Cov.: 33 AF XY: 0.00646 AC XY: 481 AN XY: 74422

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00122 Hom.: 2

Bravo AF: 0.00711

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs566932562; hg19: chr19-54695042;