dbSNP rs368933303: TSEN54:c.222-40C>G (chr17-75516969-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_207346.3(TSEN54):c.222-40C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,552,718 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.31

Publications

0 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 2A
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
pontocerebellar hypoplasia type 4
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
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

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 17-75516969-C-G is Benign according to our data. Variant chr17-75516969-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 263292.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN54	NM_207346.3 link	c.222-40C>G		intron_variant	Intron 2 of 10	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.222-40C>G		intron_variant	Intron 2 of 10	1	NM_207346.3	ENSP00000327487.6		Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000560

AC:

AN:

153612

AF XY:

0.000591

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000871

Gnomad FIN exome

AF:

0.000566

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000691

GnomAD4 exome

AF:

0.00127

AC:

1785

AN:

1400518

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

804

AN XY:

691232

show subpopulations

African (AFR)

AF:

0.000157

AC:

AN:

31828

American (AMR)

AF:

0.000110

AC:

AN:

36258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.0000277

AC:

AN:

36166

South Asian (SAS)

AF:

0.00

AC:

AN:

79828

European-Finnish (FIN)

AF:

0.000428

AC:

AN:

46748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.00152

AC:

1641

AN:

1081034

Other (OTH)

AF:

0.00196

AC:

114

AN:

58028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

237

355

474

592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.000677

AC:

103

AN:

152200

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00131

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00111

Hom.:

Bravo

AF:

0.000737

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.035

(source)

DANN

Benign

0.43

PhyloP100

-4.3

PromoterAI

-0.040

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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