Variant chr19-54191191-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.42

Variant links:

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]

TSEN34 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
TSEN34	NM_001282332.2 linkuse as main transcript	c.-5+154G>C	intron_variant	NP_001269261.1
TSEN34	NM_001282333.2 linkuse as main transcript	c.-4-170G>C	intron_variant	NP_001269262.2
TSEN34	NM_001386740.1 linkuse as main transcript	c.-4-170G>C	intron_variant	NP_001373669.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris
TSEN34	ENST00000302937.8 linkuse as main transcript	c.-4-170G>C	intron_variant	1	ENSP00000305524	P2
TSEN34	ENST00000396383.5 linkuse as main transcript	c.-5+154G>C	intron_variant	1	ENSP00000379667	P2
TSEN34	ENST00000429671.7 linkuse as main transcript	c.-4-170G>C	intron_variant	2	ENSP00000397402	P2

Frequencies

GnomAD3 genomes

AF:

0.00636

AC:

968

AN:

152098

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000558

AC XY:

334

AN XY:

599018

show subpopulations

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.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74422

show subpopulations

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.:

Bravo

AF:

0.00711

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over