Variant X-54440435-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_058163.3(TSR2):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 112,510 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TSR2
NM_058163.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365

Variant links:

Genes affected

TSR2 (HGNC:25455): (TSR2 ribosome maturation factor) The protein encoded by this gene appears to repress the transcription of NF-kappaB and may be involved in apoptosis. Defects in this gene are a cause of Diamond-Blackfan anemia. [provided by RefSeq, Oct 2016]

TSR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061198413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSR2	NM_058163.3 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/5	ENST00000375151.5	NP_477511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSR2	ENST00000375151.5 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/5	1	NM_058163.3	ENSP00000364293	P1

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34654

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1010797

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

317147

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34654

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.14C>T (p.A5V) alteration is located in exon 1 (coding exon 1) of the TSR2 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.92

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.035

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.65

M_CAP

Benign

0.0050

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.0

REVEL

Benign

0.039

Sift

Benign

0.22

Sift4G

Benign

0.39

Polyphen

0.0010

Vest4

0.035

MutPred

0.24

Loss of disorder (P = 0.0682);

MVP

0.24

MPC

0.53

ClinPred

0.079

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.038

gMVP

0.25

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