X-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAAAAAAAAAAAAAA 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 0.0081 (85 hom., 63 hem., cov: 0)
  • Exomes 𝑓: 0.0013 (9 hom. 96 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-CTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1589627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00815 (523/64175) while in subpopulation AFR AF= 0.0375 (476/12692). AF 95% confidence interval is 0.0347. There are 85 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 85 XL gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00815 AC: 523 AN: 64183 Hom.: 85 Cov.: 0 AF XY: 0.00552 AC XY: 63 AN XY: 11403

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00522

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00410

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.00644

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00132 AC: 653 AN: 494831 Hom.: 9 Cov.: 0 AF XY: 0.000660 AC XY: 96 AN XY: 145427

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00354

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.00206

Gnomad4 SAS exome AF: 0.00470

Gnomad4 FIN exome AF: 0.000380

Gnomad4 NFE exome AF: 0.000678

Gnomad4 OTH exome AF: 0.00183

GnomAD4 genome AF: 0.00815 AC: 523 AN: 64175 Hom.: 85 Cov.: 0 AF XY: 0.00553 AC XY: 63 AN XY: 11401

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.00522

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000377

Gnomad4 OTH AF: 0.00636

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 25, 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;