X-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAAAAAAAAAAAAAAA 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 0.010 (107 hom., 63 hem., cov: 0)
  • Exomes 𝑓: 0.0010 (4 hom. 93 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant X-119851748-C-CTTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1555853.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 653 AN: 64184 Hom.: 107 Cov.: 0 AF XY: 0.00553 AC XY: 63 AN XY: 11402 FAILED QC

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.00373

Gnomad AMR AF: 0.00454

Gnomad ASJ AF: 0.000500

Gnomad EAS AF: 0.000695

Gnomad SAS AF: 0.00922

Gnomad FIN AF: 0.000655

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0103

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00101 AC: 501 AN: 495271 Hom.: 4 Cov.: 0 AF XY: 0.000638 AC XY: 93 AN XY: 145739

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.000876

Gnomad4 EAS exome AF: 0.00133

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.000645

Gnomad4 NFE exome AF: 0.000389

Gnomad4 OTH exome AF: 0.00107

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0102 AC: 653 AN: 64176 Hom.: 107 Cov.: 0 AF XY: 0.00553 AC XY: 63 AN XY: 11400

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.00453

Gnomad4 ASJ AF: 0.000500

Gnomad4 EAS AF: 0.000697

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.000655

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic X-linked intellectual disability 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 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;