X-54440509-G-GGGGCCA

Variant names:

• chrX-54440509-G-GGGGCCA
• rs765357489
• NM_058163.3:c.81+18_81+23dupCAGGGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000375151.5(TSR2):​c.81+7_81+8insGGGCCA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000605 in 1,140,587 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000062 (0 hom. 15 hem.)
• Consequence: TSR2 ENST00000375151.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.810

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-54440509-G-GGGGCCA is Benign according to our data. Variant chrX-54440509-G-GGGGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 3716930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSR2	NM_058163.3	c.81+18_81+23dupCAGGGC		intron_variant	Intron 1 of 4	ENST00000375151.5	NP_477511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSR2	ENST00000375151.5	c.81+7_81+8insGGGCCA		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_058163.3	ENSP00000364293.4

Frequencies

GnomAD3 genomes AF: 0.0000446 AC: 5 AN: 112165 Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1 AN XY: 34335

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000943

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: 0.0000752

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000303 AC: 3 AN: 98933 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17431

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000119

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000451

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000622 AC: 64 AN: 1028422 Hom.: 0 Cov.: 29 AF XY: 0.0000468 AC XY: 15 AN XY: 320682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000217

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000265

Gnomad4 NFE exome AF: 0.0000692

Gnomad4 OTH exome AF: 0.0000232

GnomAD4 genome AF: 0.0000446 AC: 5 AN: 112165 Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1 AN XY: 34335

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000943

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000752

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765357489; hg19: chrX-54466942;