X-119851748-CTTTTT-CTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_080632.3(UPF3B):​c.263+16_263+18dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00064 (1 hom., 8 hem., cov: 0)
  • Exomes 𝑓: 0.00075 (6 hom. 17 hem.)
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Not reported in ClinVar
• 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000638 (41/64217) while in subpopulation AFR AF= 0.00283 (36/12724). AF 95% confidence interval is 0.0021. There are 1 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.263+16_263+18dupAAA		intron_variant		ENST00000276201.7	NP_542199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7	c.263+18_263+19insAAA		intron_variant		1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.263+18_263+19insAAA		intron_variant		1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 41 AN: 64225 Hom.: 1 Cov.: 0 AF XY: 0.000702 AC XY: 8 AN XY: 11403

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00208

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000655

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00128

GnomAD4 exome AF: 0.000753 AC: 373 AN: 495092 Hom.: 6 Cov.: 0 AF XY: 0.000117 AC XY: 17 AN XY: 145536

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.000350

Gnomad4 EAS exome AF: 0.000732

Gnomad4 SAS exome AF: 0.000486

Gnomad4 FIN exome AF: 0.000418

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.000638 AC: 41 AN: 64217 Hom.: 1 Cov.: 0 AF XY: 0.000702 AC XY: 8 AN XY: 11401

Gnomad4 AFR AF: 0.00283

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00209

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000655

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00127

ClinVar

Not reported in ClinVar

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;