Genetic Variant TSEN34:c.-5+75C>T (chr19-54190237-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.52

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=-0.74).

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	Effect	Exon rank	Protein	UniProt
TSEN34	XM_011527294.4 link	c.-5+75C>T	intron_variant	Intron 1 of 4	XP_011525596.1	Q9BSV6A0A024R4N9
TSEN34	XM_047439391.1 link	c.-5+641C>T	intron_variant	Intron 1 of 4	XP_047295347.1
TSEN34	NM_001282333.2 link	c.-139C>T	upstream_gene_variant		NP_001269262.2	E7EQB3B4DT51

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TSEN34	ENST00000455798.6 link	c.-5+75C>T	intron_variant	Intron 1 of 4	2	ENSP00000400743.2	Q9BSV6B0V3J0
TSEN34	ENST00000302937.8 link	c.-218C>T	upstream_gene_variant		1	ENSP00000305524.4	Q9BSV6
TSEN34	ENST00000667261.1 link	c.-139C>T	upstream_gene_variant			ENSP00000499595.1	A0A590UJW4

Frequencies

GnomAD3 genomes

AF:

0.0452

AC:

6868

AN:

151872

Hom.:

299

Cov.:

show subpopulations

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.:

AF XY:

0.0177

AC XY:

6694

AN XY:

377982

show subpopulations

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.:

AF XY:

0.0457

AC XY:

3392

AN XY:

74300

show subpopulations

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.:

Bravo

AF:

0.0503

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

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