Genetic Variant TSR2:p.Glu21Gln (chrX-54440482-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_058163.3(TSR2):c.61G>C(p.Glu21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.7e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

TSR2
NM_058163.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Diamond-Blackfan anemia 14 with mandibulofacial dysostosis
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

TSR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17942917).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058163.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSR2	NM_058163.3	MANE Select	c.61G>C	p.Glu21Gln	missense	Exon 1 of 5	NP_477511.1	Q969E8
TSR2	NM_001346789.2		c.61G>C	p.Glu21Gln	missense	Exon 1 of 5	NP_001333718.1
TSR2	NM_001346790.2		c.-327G>C		5_prime_UTR	Exon 1 of 5	NP_001333719.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSR2	ENST00000375151.5	TSL:1 MANE Select	c.61G>C	p.Glu21Gln	missense	Exon 1 of 5	ENSP00000364293.4	Q969E8
TSR2	ENST00000908048.1		c.61G>C	p.Glu21Gln	missense	Exon 1 of 5	ENSP00000578107.1
TSR2	ENST00000960847.1		c.61G>C	p.Glu21Gln	missense	Exon 1 of 5	ENSP00000630906.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.74e-7

AC:

AN:

1026349

Hom.:

Cov.:

AF XY:

0.00000309

AC XY:

AN XY:

323777

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23256

American (AMR)

AF:

0.00

AC:

AN:

22672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15223

East Asian (EAS)

AF:

0.0000359

AC:

AN:

27842

South Asian (SAS)

AF:

0.00

AC:

AN:

43910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3805

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

809297

Other (OTH)

AF:

0.00

AC:

AN:

42852

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.67

M_CAP

Benign

0.057

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

1.8

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.27

REVEL

Benign

0.070

Sift

Benign

0.18

Sift4G

Benign

0.44

Polyphen

0.030

Vest4

0.24

MutPred

0.49

Gain of MoRF binding (P = 0.0523)

MVP

0.12

MPC

0.54

ClinPred

0.13

GERP RS

3.6

PromoterAI

0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.44

Mutation Taster

=99/1

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over