rs773655172

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001346790.2(TSR2):c.-245G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,202,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 125 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 118 hem. )

Consequence

TSR2
NM_001346790.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011079967).

BP6

Variant X-54440751-G-A is Benign according to our data. Variant chrX-54440751-G-A is described in ClinVar as Benign. ClinVar VariationId is 2150704.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 12 AD,XL gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346790.2. 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.143G>A	p.Gly48Asp	missense	Exon 2 of 5	NP_477511.1	Q969E8
TSR2	NM_001346790.2		c.-245G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001333719.1
TSR2	NM_001346791.2		c.-254G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001333720.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSR2	ENST00000375151.5	TSL:1 MANE Select	c.143G>A	p.Gly48Asp	missense	Exon 2 of 5	ENSP00000364293.4	Q969E8
TSR2	ENST00000908048.1		c.143G>A	p.Gly48Asp	missense	Exon 2 of 5	ENSP00000578107.1
TSR2	ENST00000960847.1		c.143G>A	p.Gly48Asp	missense	Exon 2 of 5	ENSP00000630906.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111731

Hom.:

Cov.:

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:

0.00451

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000343

AC:

AN:

169278

AF XY:

0.000560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000182

AC:

198

AN:

1090453

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

118

AN XY:

356545

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26144

American (AMR)

AF:

0.00

AC:

AN:

34161

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18837

East Asian (EAS)

AF:

0.00

AC:

AN:

29912

South Asian (SAS)

AF:

0.00360

AC:

190

AN:

52744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4081

European-Non Finnish (NFE)

AF:

0.00000239

AC:

AN:

838562

Other (OTH)

AF:

0.000131

AC:

AN:

45728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000107

AC:

AN:

111785

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

33947

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30851

American (AMR)

AF:

0.00

AC:

AN:

10529

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3526

South Asian (SAS)

AF:

0.00452

AC:

AN:

2654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53086

Other (OTH)

AF:

0.00

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000149

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000511

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.27

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.53

M_CAP

Benign

0.0058

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

1.2

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

REVEL

Benign

0.17

Sift

Benign

0.69

Sift4G

Benign

1.0

Polyphen

0.0070

Vest4

0.095

MutPred

0.69

Loss of ubiquitination at K44 (P = 0.1441)

MVP

0.21

MPC

0.79

ClinPred

0.044

GERP RS

1.1

PromoterAI

-0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.64

Mutation Taster

=93/7

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over