chr19-54193391-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001077446.4(TSEN34):c.*29G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,706 control chromosomes in the GnomAD database, including 737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 117 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 620 hom. )

Consequence

TSEN34
NM_001077446.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.113

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 2C
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN34 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-54193391-G-A is Benign according to our data. Variant chr19-54193391-G-A is described in CliVar as Benign. Clinvar id is 261679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54193391-G-A is described in CliVar as Benign. Clinvar id is 261679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34	NM_001077446.4 link	c.*29G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000396388.3	NP_001070914.1	Q9BSV6A0A024R4N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000396388.3 link	c.*29G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_001077446.4	ENSP00000379671.2		Q9BSV6

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3625

AN:

152166

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0211

AC:

5234

AN:

248252

AF XY:

0.0178

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0310

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.00856

AC:

12509

AN:

1461422

Hom.:

620

Cov.:

AF XY:

0.00811

AC XY:

5895

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.0519

AC:

1736

AN:

33450

American (AMR)

AF:

0.0287

AC:

1282

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00268

AC:

AN:

26116

East Asian (EAS)

AF:

0.151

AC:

6001

AN:

39672

South Asian (SAS)

AF:

0.00347

AC:

299

AN:

86208

European-Finnish (FIN)

AF:

0.0292

AC:

1561

AN:

53382

Middle Eastern (MID)

AF:

0.00313

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000623

AC:

693

AN:

1111796

Other (OTH)

AF:

0.0141

AC:

849

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

741

1481

2222

2962

3703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

174

348

522

696

870

<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:

0.0239

AC:

3638

AN:

152284

Hom.:

117

Cov.:

AF XY:

0.0250

AC XY:

1863

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0510

AC:

2119

AN:

41560

American (AMR)

AF:

0.0183

AC:

280

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

683

AN:

5180

South Asian (SAS)

AF:

0.00911

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0302

AC:

320

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

68016

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

168

336

504

672

840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00929

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0700

AC:

243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 06, 2018

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pontoneocerebellar hypoplasia

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.52

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over