X-119851748-CTTTTT-CTTTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAAAAA 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 0.030 (127 hom., 334 hem., cov: 0)
  • Exomes 𝑓: 0.010 (102 hom. 383 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 Benign. Variant got -10 ACMG points.

• BP6: Variant X-119851748-C-CTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1594434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 1927 AN: 64116 Hom.: 127 Cov.: 0 AF XY: 0.0293 AC XY: 334 AN XY: 11400

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0506

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.00524

Gnomad MID AF: 0.0370

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0398

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0102 AC: 4940 AN: 485605 Hom.: 102 Cov.: 0 AF XY: 0.00273 AC XY: 383 AN XY: 140405

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.0565

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.00634

Gnomad4 NFE exome AF: 0.00733

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0301 AC: 1927 AN: 64108 Hom.: 127 Cov.: 0 AF XY: 0.0293 AC XY: 334 AN XY: 11398

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0506

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0666

Gnomad4 FIN AF: 0.00524

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0406

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 29, 2024

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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: rs55712755; hg19: chrX-118985711;