chrX-54440632-C-T

Variant names:

• chrX-54440632-C-T
• rs7066917
• NM_058163.3:c.82-58C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.81
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1269390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSR2	NM_058163.3	MANE Select	c.82-58C>T		intron	N/A	NP_477511.1	Q969E8
	TSR2	NM_001346789.2		c.82-58C>T		intron	N/A	NP_001333718.1
	TSR2	NM_001346790.2		c.-306-58C>T		intron	N/A	NP_001333719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSR2	ENST00000375151.5	TSL:1 MANE Select	c.82-58C>T		intron	N/A	ENSP00000364293.4	Q969E8
	TSR2	ENST00000908048.1		c.82-58C>T		intron	N/A	ENSP00000578107.1
	TSR2	ENST00000960847.1		c.82-58C>T		intron	N/A	ENSP00000630906.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 8401 AN: 111613 Hom.: 631 Cov.: 23

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

African (AFR) AF: 0.252 AC: 6420 AN: 25523

American (AMR) AF: 0.0186 AC: 611 AN: 32785

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 223 AN: 18725

East Asian (EAS) AF: 0.0000338 AC: 1 AN: 29591

South Asian (SAS) AF: 0.0127 AC: 650 AN: 51341

European-Finnish (FIN) AF: 0.00571 AC: 227 AN: 39724

Middle Eastern (MID) AF: 0.0473 AC: 189 AN: 3995

European-Non Finnish (NFE) AF: 0.0132 AC: 10558 AN: 800451

Other (OTH) AF: 0.0285 AC: 1266 AN: 44359

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

African (AFR) AF: 0.233 AC: 7134 AN: 30604

American (AMR) AF: 0.0316 AC: 334 AN: 10570

Ashkenazi Jewish (ASJ) AF: 0.00793 AC: 21 AN: 2649

East Asian (EAS) AF: 0.000283 AC: 1 AN: 3539

South Asian (SAS) AF: 0.00821 AC: 22 AN: 2681

European-Finnish (FIN) AF: 0.00395 AC: 24 AN: 6069

Middle Eastern (MID) AF: 0.0605 AC: 13 AN: 215

European-Non Finnish (NFE) AF: 0.0144 AC: 767 AN: 53130

Other (OTH) AF: 0.0654 AC: 100 AN: 1529

Alfa AF: 0.0409 Hom.: 3503

Bravo AF: 0.0856

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.99
DANN	Benign	0.64
PhyloP100		-1.8
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7066917; hg19: chrX-54467065;