rs191600766

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_207346.3(TSEN54):c.624-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,609,530 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 Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 4 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.255

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 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

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 17-75521674-A-G is Benign according to our data. Variant chr17-75521674-A-G is described in ClinVar as Benign. ClinVar VariationId is 263296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000887 (135/152262) while in subpopulation AMR AF = 0.00274 (42/15302). AF 95% confidence interval is 0.00209. There are 1 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

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.624-31A>G		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.624-31A>G	intron	N/A	ENSP00000327487.6	Q7Z6J9-1
TSEN54	ENST00000680999.1		c.624-31A>G	intron	N/A	ENSP00000504984.1	A0A7P0Z413
TSEN54	ENST00000915433.1		c.624-31A>G	intron	N/A	ENSP00000585492.1

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00116

AC:

288

AN:

248736

AF XY:

0.00134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.000882

AC:

1285

AN:

1457268

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

686

AN XY:

725238

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33374

American (AMR)

AF:

0.00190

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00311

AC:

AN:

26082

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39672

South Asian (SAS)

AF:

0.00154

AC:

133

AN:

86184

European-Finnish (FIN)

AF:

0.0000759

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5760

European-Non Finnish (NFE)

AF:

0.000594

AC:

659

AN:

1108516

Other (OTH)

AF:

0.00199

AC:

120

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.000887

AC:

135

AN:

152262

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41548

American (AMR)

AF:

0.00274

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68018

Other (OTH)

AF:

0.00238

AC:

AN:

2104

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:

0.00201

Hom.:

Bravo

AF:

0.00131

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.26

BranchPoint Hunter

4.0

Mutation Taster

=100/0

polymorphism

(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