17-75522247-A-C

Position:

chr17-75522247-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207346.3(TSEN54):c.1166A>C(p.Gln389Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 1,547,262 control chromosomes in the GnomAD database, including 7,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 711 hom., cov: 32)

Exomes 𝑓: 0.095 ( 6631 hom. )

Consequence

TSEN54
NM_207346.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.412

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018183887).

BP6

Variant 17-75522247-A-C is Benign according to our data. Variant chr17-75522247-A-C is described in ClinVar as [Benign]. Clinvar id is 96672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75522247-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.1166A>C	p.Gln389Pro	missense_variant	8/11	ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.1166A>C	p.Gln389Pro	missense_variant	8/11	1	NM_207346.3	ENSP00000327487	P1	Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14199

AN:

152154

Hom.:

707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0751

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.0796

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0937

GnomAD3 exomes

AF:

0.0778

AC:

11366

AN:

146068

Hom.:

528

AF XY:

0.0778

AC XY:

6112

AN XY:

78546

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.0758

Gnomad EAS exome

AF:

0.000748

Gnomad SAS exome

AF:

0.0689

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0835

GnomAD4 exome

AF:

0.0946

AC:

131976

AN:

1394990

Hom.:

6631

Cov.:

AF XY:

0.0938

AC XY:

64468

AN XY:

687646

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0527

Gnomad4 ASJ exome

AF:

0.0769

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.0680

Gnomad4 FIN exome

AF:

0.0845

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0840

GnomAD4 genome

AF:

0.0934

AC:

14217

AN:

152272

Hom.:

711

Cov.:

AF XY:

0.0910

AC XY:

6777

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0749

Gnomad4 ASJ

AF:

0.0703

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0696

Gnomad4 FIN

AF:

0.0796

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0937

Alfa

AF:

0.0825

Hom.:

203

Bravo

AF:

0.0924

TwinsUK

AF:

0.105

AC:

390

ALSPAC

AF:

0.0965

AC:

372

ESP6500AA

AF:

0.0733

AC:

290

ESP6500EA

AF:

0.0677

AC:

522

ExAC

AF:

0.0333

AC:

2844

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 12, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Pontoneocerebellar hypoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

5.8

DANN

Benign

0.40

DEOGEN2

Benign

0.016

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.067

Sift

Benign

0.17

Sift4G

Benign

0.24

Polyphen

0.13

Vest4

0.068

MPC

0.35

ClinPred

0.0039

GERP RS

-0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.65

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