dbSNP rs56895494: TSEN54:c.370-19C>A (chr17-75517538-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_207346.3(TSEN54):c.370-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,605,770 control chromosomes in the GnomAD database, including 13,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1141 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12357 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0230

Publications

5 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

new If you want to explore the variant's impact on the transcript NM_207346.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.7).

BP6

Variant 17-75517538-C-A is Benign according to our data. Variant chr17-75517538-C-A is described in ClinVar as Benign. ClinVar VariationId is 137757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 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.370-19C>A		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.370-19C>A	intron	N/A	ENSP00000327487.6	Q7Z6J9-1
TSEN54	ENST00000680999.1		c.370-19C>A	intron	N/A	ENSP00000504984.1	A0A7P0Z413
TSEN54	ENST00000915433.1		c.370-19C>A	intron	N/A	ENSP00000585492.1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18206

AN:

152002

Hom.:

1140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.115

AC:

28915

AN:

250960

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.127

AC:

185288

AN:

1453650

Hom.:

12357

Cov.:

AF XY:

0.127

AC XY:

91932

AN XY:

723670

show subpopulations

African (AFR)

AF:

0.119

AC:

3966

AN:

33298

American (AMR)

AF:

0.0723

AC:

3232

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4238

AN:

26098

East Asian (EAS)

AF:

0.0181

AC:

718

AN:

39652

South Asian (SAS)

AF:

0.0989

AC:

8511

AN:

86092

European-Finnish (FIN)

AF:

0.115

AC:

6089

AN:

52836

Middle Eastern (MID)

AF:

0.145

AC:

832

AN:

5756

European-Non Finnish (NFE)

AF:

0.136

AC:

150376

AN:

1105088

Other (OTH)

AF:

0.122

AC:

7326

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8545

17091

25636

34182

42727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5172

10344

15516

20688

25860

<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:

0.120

AC:

18220

AN:

152120

Hom.:

1141

Cov.:

AF XY:

0.118

AC XY:

8763

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.114

AC:

4749

AN:

41504

American (AMR)

AF:

0.101

AC:

1542

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

550

AN:

3468

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5182

South Asian (SAS)

AF:

0.100

AC:

481

AN:

4808

European-Finnish (FIN)

AF:

0.108

AC:

1147

AN:

10590

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9303

AN:

67972

Other (OTH)

AF:

0.129

AC:

273

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

816

1633

2449

3266

4082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.135

Hom.:

268

Bravo

AF:

0.117

Asia WGS

AF:

0.0740

AC:

260

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.2

(source)

DANN

Benign

0.77

PhyloP100

0.023

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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