Genetic Variant TSR2:p.Ala8Ser (chrX-54440443-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_058163.3(TSR2):c.22G>T(p.Ala8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000985 in 1,014,796 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.9e-7 ( 0 hom. 1 hem. )

Consequence

TSR2
NM_058163.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025972664).

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.22G>T	p.Ala8Ser	missense	Exon 1 of 5	NP_477511.1	Q969E8
TSR2	NM_001346789.2		c.22G>T	p.Ala8Ser	missense	Exon 1 of 5	NP_001333718.1
TSR2	NM_001346790.2		c.-366G>T		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.22G>T	p.Ala8Ser	missense	Exon 1 of 5	ENSP00000364293.4	Q969E8
TSR2	ENST00000908048.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 5	ENSP00000578107.1
TSR2	ENST00000960847.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 5	ENSP00000630906.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.85e-7

AC:

AN:

1014796

Hom.:

Cov.:

AF XY:

0.00000313

AC XY:

AN XY:

319726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22829

American (AMR)

AF:

0.00

AC:

AN:

20476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14577

East Asian (EAS)

AF:

0.00

AC:

AN:

27258

South Asian (SAS)

AF:

0.0000238

AC:

AN:

42004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36629

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

804884

Other (OTH)

AF:

0.00

AC:

AN:

42357

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.00024

LIST_S2

Benign

0.51

M_CAP

Benign

0.035

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.51

PhyloP100

-0.65

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.22

REVEL

Benign

0.022

Sift

Benign

0.89

Sift4G

Benign

0.83

Polyphen

0.0

Vest4

0.059

MutPred

0.37

Gain of glycosylation at A8 (P = 0.0183)

MVP

0.043

MPC

0.49

ClinPred

0.062

GERP RS

-0.54

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.054

gMVP

0.13

Mutation Taster

=100/0

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