dbSNP rs57636645: TSEN54:c.521+39C>T (chr17-75519086-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_207346.3(TSEN54):c.521+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,610,374 control chromosomes in the GnomAD database, including 1,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 883 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 851 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0350

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pontocerebellar hypoplasia type 4
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 17-75519086-C-T is Benign according to our data. Variant chr17-75519086-C-T is described in ClinVar as Benign. ClinVar VariationId is 160135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	NM_207346.3	MANE Select	c.521+39C>T		intron	N/A	NP_997229.2	Q7Z6J9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.521+39C>T	intron	N/A	ENSP00000327487.6	Q7Z6J9-1
TSEN54	ENST00000680999.1		c.521+39C>T	intron	N/A	ENSP00000504984.1	A0A7P0Z413
TSEN54	ENST00000915433.1		c.521+39C>T	intron	N/A	ENSP00000585492.1

Frequencies

GnomAD3 genomes

AF:

0.0602

AC:

9146

AN:

151910

Hom.:

879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.0489

GnomAD2 exomes

AF:

0.0165

AC:

4145

AN:

251488

AF XY:

0.0121

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00659

AC:

9604

AN:

1458346

Hom.:

851

Cov.:

AF XY:

0.00569

AC XY:

4131

AN XY:

725740

show subpopulations

African (AFR)

AF:

0.215

AC:

7181

AN:

33406

American (AMR)

AF:

0.0150

AC:

670

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00337

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000545

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000635

AC:

704

AN:

1108808

Other (OTH)

AF:

0.0141

AC:

847

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

424

849

1273

1698

2122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0603

AC:

9164

AN:

152028

Hom.:

883

Cov.:

AF XY:

0.0584

AC XY:

4338

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.205

AC:

8493

AN:

41386

American (AMR)

AF:

0.0299

AC:

456

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00125

AC:

AN:

68012

Other (OTH)

AF:

0.0484

AC:

102

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

358

716

1073

1431

1789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0310

Hom.:

148

Bravo

AF:

0.0692

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.035

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over