Variant rs191600766 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

TSEN54 (HGNC:):

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 4 / 10). 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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.624-31A>G		intron_variant		ENST00000333213.11	NP_997229.2	Q7Z6J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.624-31A>G		intron_variant		1	NM_207346.3	ENSP00000327487.6		Q7Z6J9-1

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

GnomAD3 exomes

AF:

0.00116

AC:

288

AN:

248736

Hom.:

AF XY:

0.00134

AC XY:

181

AN XY:

134778

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 SAS exome

AF:

0.00147

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

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00311

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.0000759

Gnomad4 NFE exome

AF:

0.000594

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.000887

AC:

135

AN:

152262

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00131

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.81

BranchPoint Hunter

4.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over