X-54440632-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058163.3(TSR2):c.82-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 1,158,160 control chromosomes in the GnomAD database, including 1,317 homozygotes. There are 8,232 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (634 hom., 2257 hem., cov: 23)
  • Exomes 𝑓: 0.019 (683 hom. 5975 hem.)
• Consequence: TSR2 NM_058163.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-54440632-C-T is Benign according to our data. Variant chrX-54440632-C-T is described in ClinVar as [Benign]. Clinvar id is 1269390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSR2	NM_058163.3	c.82-58C>T		intron_variant		ENST00000375151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSR2	ENST00000375151.5	c.82-58C>T		intron_variant		1	NM_058163.3	P1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 8401 AN: 111613 Hom.: 631 Cov.: 23 AF XY: 0.0662 AC XY: 2238 AN XY: 33801

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0191

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.00793

Gnomad EAS AF: 0.000282

Gnomad SAS AF: 0.00818

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.0551

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0662

GnomAD4 exome AF: 0.0192 AC: 20145 AN: 1046494 Hom.: 683 Cov.: 23 AF XY: 0.0187 AC XY: 5975 AN XY: 319360

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0000338

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.00571

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0285

GnomAD4 genome AF: 0.0755 AC: 8429 AN: 111666 Hom.: 634 Cov.: 23 AF XY: 0.0666 AC XY: 2257 AN XY: 33864

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.00793

Gnomad4 EAS AF: 0.000283

Gnomad4 SAS AF: 0.00821

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0226 Hom.: 1267

Bravo AF: 0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.99
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs7066917; hg19: chrX-54467065;