X-119851748-CTTTTT-CTTTTTTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00093 (4 hom., 9 hem., cov: 0)
  • Exomes 𝑓: 0.014 (96 hom. 648 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0650

Genes affected

UPF3B (HGNC:20439): (UPF3B regulator of nonsense mediated mRNA decay) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome X. Two splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant X-119851748-C-CTTTTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1615705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF3B	NM_080632.3	c.263+18_263+19insAAAAAAAAAAA		intron_variant		ENST00000276201.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF3B	ENST00000276201.7	c.263+18_263+19insAAAAAAAAAAA		intron_variant		1	NM_080632.3	A1
UPF3B	ENST00000345865.6	c.263+18_263+19insAAAAAAAAAAA		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 60 AN: 64221 Hom.: 4 Cov.: 0 AF XY: 0.000789 AC XY: 9 AN XY: 11403 FAILED QC

Gnomad AFR AF: 0.00260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000680

Gnomad ASJ AF: 0.000500

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000579

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0142 AC: 6759 AN: 475665 Hom.: 96 Cov.: 0 AF XY: 0.00475 AC XY: 648 AN XY: 136407

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.0374

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.0501

Gnomad4 SAS exome AF: 0.0169

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000934 AC: 60 AN: 64213 Hom.: 4 Cov.: 0 AF XY: 0.000789 AC XY: 9 AN XY: 11401

Gnomad4 AFR AF: 0.00259

Gnomad4 AMR AF: 0.000680

Gnomad4 ASJ AF: 0.000500

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Syndromic X-linked intellectual disability 14 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 29, 2024	- -

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: rs55712755; hg19: chrX-118985711;