Variant chrX-54443461-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_058163.3(TSR2):c.234T>C(p.Asp78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,205,507 control chromosomes in the GnomAD database, including 15 homozygotes. There are 1,772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 0 hom., 166 hem., cov: 23)

Exomes 𝑓: 0.0043 ( 15 hom. 1606 hem. )

Consequence

TSR2
NM_058163.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.69

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-54443461-T-C is Benign according to our data. Variant chrX-54443461-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 709009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-54443461-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00431 (4716/1093692) while in subpopulation MID AF= 0.0274 (113/4119). AF 95% confidence interval is 0.0233. There are 15 homozygotes in gnomad4_exome. There are 1606 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 166 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSR2	NM_058163.3 linkuse as main transcript	c.234T>C	p.Asp78=	synonymous_variant	3/5	ENST00000375151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSR2	ENST00000375151.5 linkuse as main transcript	c.234T>C	p.Asp78=	synonymous_variant	3/5	1	NM_058163.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

520

AN:

111760

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

166

AN XY:

33924

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.00783

Gnomad ASJ

AF:

0.00792

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00460

Gnomad MID

AF:

0.0292

Gnomad NFE

AF:

0.00609

Gnomad OTH

AF:

0.00659

GnomAD3 exomes

AF:

0.00450

AC:

790

AN:

175563

Hom.:

AF XY:

0.00482

AC XY:

291

AN XY:

60431

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.00690

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00165

Gnomad FIN exome

AF:

0.00572

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.00888

GnomAD4 exome

AF:

0.00431

AC:

4716

AN:

1093692

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

1606

AN XY:

359390

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00339

Gnomad4 ASJ exome

AF:

0.00799

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.00645

Gnomad4 NFE exome

AF:

0.00435

Gnomad4 OTH exome

AF:

0.00581

GnomAD4 genome

AF:

0.00463

AC:

518

AN:

111815

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

166

AN XY:

33989

show subpopulations

Gnomad4 AFR

AF:

0.000974

Gnomad4 AMR

AF:

0.00782

Gnomad4 ASJ

AF:

0.00792

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00188

Gnomad4 FIN

AF:

0.00460

Gnomad4 NFE

AF:

0.00609

Gnomad4 OTH

AF:

0.00651

Alfa

AF:

0.00623

Hom.:

Bravo

AF:

0.00527

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TSR2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Diamond-Blackfan anemia 14 with mandibulofacial dysostosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.3

DANN

Benign

0.67

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