X-54443504-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_058163.3(TSR2):c.264+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000822 in 1,143,128 control chromosomes in the GnomAD database, including 1 homozygotes. There are 34 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 0.00015 (0 hom., 9 hem., cov: 23)
  • Exomes 𝑓: 0.000075 (1 hom. 25 hem.)
• Consequence: TSR2 NM_058163.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-54443504-C-T is Benign according to our data. Variant chrX-54443504-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2860744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSR2	NM_058163.3	c.264+13C>T		intron_variant		ENST00000375151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSR2	ENST00000375151.5	c.264+13C>T		intron_variant		1	NM_058163.3	P1

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 17 AN: 112164 Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9 AN XY: 34316

Gnomad AFR AF: 0.000195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000757

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000101 AC: 16 AN: 158627 Hom.: 1 AF XY: 0.0000206 AC XY: 1 AN XY: 48515

Gnomad AFR exome AF: 0.000169

Gnomad AMR exome AF: 0.000457

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000410

Gnomad OTH exome AF: 0.000265

GnomAD4 exome AF: 0.0000747 AC: 77 AN: 1030964 Hom.: 1 Cov.: 23 AF XY: 0.0000817 AC XY: 25 AN XY: 305886

Gnomad4 AFR exome AF: 0.000286

Gnomad4 AMR exome AF: 0.000446

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000595

Gnomad4 OTH exome AF: 0.0000686

GnomAD4 genome AF: 0.000152 AC: 17 AN: 112164 Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9 AN XY: 34316

Gnomad4 AFR AF: 0.000195

Gnomad4 AMR AF: 0.000757

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000563

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000869 Hom.: 1

Bravo AF: 0.000204

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs368362985; hg19: chrX-54469937;