NM_058163.3:c.45G>T

Variant names:

• chrX-54440466-G-T
• NM_058163.3:c.45G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_058163.3(TSR2):​c.45G>T​(p.Gly15Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TSR2 NM_058163.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.84
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-3.84 with no splicing effect.

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.45G>T	p.Gly15Gly	synonymous	Exon 1 of 5	NP_477511.1	Q969E8
	TSR2	NM_001346789.2		c.45G>T	p.Gly15Gly	synonymous	Exon 1 of 5	NP_001333718.1
	TSR2	NM_001346790.2		c.-343G>T		5_prime_UTR	Exon 1 of 5	NP_001333719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSR2	ENST00000375151.5	TSL:1 MANE Select	c.45G>T	p.Gly15Gly	synonymous	Exon 1 of 5	ENSP00000364293.4	Q969E8
	TSR2	ENST00000908048.1		c.45G>T	p.Gly15Gly	synonymous	Exon 1 of 5	ENSP00000578107.1
	TSR2	ENST00000960847.1		c.45G>T	p.Gly15Gly	synonymous	Exon 1 of 5	ENSP00000630906.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1020377 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 321195

African (AFR) AF: 0.00 AC: 0 AN: 23002

American (AMR) AF: 0.00 AC: 0 AN: 21813

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14882

East Asian (EAS) AF: 0.00 AC: 0 AN: 27541

South Asian (SAS) AF: 0.00 AC: 0 AN: 42905

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3775

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806828

Other (OTH) AF: 0.00 AC: 0 AN: 42573

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-3.8
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

hg19: chrX-54466899;