Variant 17-75516562-T-TGGAGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BA1

The NM_207346.3(TSEN54):c.3_8dup(p.Glu6_Pro7dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,141,802 control chromosomes in the GnomAD database, including 2,608 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.070 ( 424 hom., cov: 32)

Exomes 𝑓: 0.065 ( 2184 hom. )

Consequence

TSEN54
NM_207346.3 inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:8

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_207346.3.

BP6

Variant 17-75516562-T-TGGAGCC is Benign according to our data. Variant chr17-75516562-T-TGGAGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 96674.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=5, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.3_8dup	p.Glu6_Pro7dup	inframe_insertion	1/11	ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.3_8dup	p.Glu6_Pro7dup	inframe_insertion	1/11	1	NM_207346.3	ENSP00000327487	P1	Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10382

AN:

149324

Hom.:

423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.0749

Gnomad AMR

AF:

0.0635

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.000783

Gnomad SAS

AF:

0.0826

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0679

Gnomad OTH

AF:

0.0697

GnomAD4 exome

AF:

0.0647

AC:

64199

AN:

992370

Hom.:

2184

Cov.:

AF XY:

0.0644

AC XY:

30073

AN XY:

467008

show subpopulations

Gnomad4 AFR exome

AF:

0.0861

Gnomad4 AMR exome

AF:

0.0613

Gnomad4 ASJ exome

AF:

0.0536

Gnomad4 EAS exome

AF:

0.000468

Gnomad4 SAS exome

AF:

0.0784

Gnomad4 FIN exome

AF:

0.0648

Gnomad4 NFE exome

AF:

0.0651

Gnomad4 OTH exome

AF:

0.0667

GnomAD4 genome

AF:

0.0695

AC:

10389

AN:

149432

Hom.:

424

Cov.:

AF XY:

0.0690

AC XY:

5030

AN XY:

72914

show subpopulations

Gnomad4 AFR

AF:

0.0824

Gnomad4 AMR

AF:

0.0635

Gnomad4 ASJ

AF:

0.0645

Gnomad4 EAS

AF:

0.000785

Gnomad4 SAS

AF:

0.0835

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0679

Gnomad4 OTH

AF:

0.0689

Alfa

AF:

0.0688

Hom.:

Asia WGS

AF:

0.0310

AC:

AN:

3158

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:4

Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Jan 08, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 26, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 08, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 05, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 11, 2019	- -

Pontoneocerebellar hypoplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pontocerebellar hypoplasia type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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