17-75516562-T-TGGAGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM4BP6BA1

The NM_207346.3(TSEN54):c.3_8dupGGAGCC(p.Pro3_Glu4insGluPro) variant causes a disruptive 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). Synonymous variant affecting the same amino acid position (i.e. P3P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.070 ( 424 hom., cov: 32)

Exomes 𝑓: 0.065 ( 2184 hom. )

Consequence

TSEN54
NM_207346.3 disruptive_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 was made for transcript

Our verdict: Benign. The variant received -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: {Uncertain_significance=1, Likely_benign=2, Benign=5}.

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 rank	MANE	Protein	UniProt
TSEN54	NM_207346.3 link	c.3_8dupGGAGCC	p.Pro3_Glu4insGluPro	disruptive_inframe_insertion	Exon 1 of 11	ENST00000333213.11	NP_997229.2	Q7Z6J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 link	c.3_8dupGGAGCC	p.Pro3_Glu4insGluPro	disruptive_inframe_insertion	Exon 1 of 11	1	NM_207346.3	ENSP00000327487.6		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

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

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

AC:

1693

AN:

19654

Gnomad4 AMR exome

AF:

0.0613

AC:

334

AN:

5450

Gnomad4 ASJ exome

AF:

0.0536

AC:

565

AN:

10536

Gnomad4 EAS exome

AF:

0.000468

AC:

AN:

17080

Gnomad4 SAS exome

AF:

0.0784

AC:

1471

AN:

18764

Gnomad4 FIN exome

AF:

0.0648

AC:

1045

AN:

16120

Gnomad4 NFE exome

AF:

0.0651

AC:

56353

AN:

865050

Gnomad4 Remaining exome

AF:

0.0667

AC:

2487

AN:

37282

Heterozygous variant carriers

3166

6333

9499

12666

15832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2636

5272

7908

10544

13180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.0824211

AN:

0.0824211

Gnomad4 AMR

AF:

0.0635

AC:

0.0634636

AN:

0.0634636

Gnomad4 ASJ

AF:

0.0645

AC:

0.0644691

AN:

0.0644691

Gnomad4 EAS

AF:

0.000785

AC:

0.000785238

AN:

0.000785238

Gnomad4 SAS

AF:

0.0835

AC:

0.0835064

AN:

0.0835064

Gnomad4 FIN

AF:

0.0660

AC:

0.0659772

AN:

0.0659772

Gnomad4 NFE

AF:

0.0679

AC:

0.0678826

AN:

0.0678826

Gnomad4 OTH

AF:

0.0689

AC:

0.0689489

AN:

0.0689489

Heterozygous variant carriers

489

978

1466

1955

2444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jun 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 05, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 08, 2014

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 08, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pontoneocerebellar hypoplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pontocerebellar hypoplasia type 4

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=130/70

polymorphism (auto)

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