chrX-119851748-CTTTTT-C

Position:

• chrX-119851748-CTTTTT-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_080632.3(UPF3B):​c.263+14_263+18delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 495,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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 -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000127 (63/495297) while in subpopulation AMR AF= 0.000164 (2/12180). AF 95% confidence interval is 0.000117. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.263+14_263+18delAAAAA		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+14_263+18delAAAAA		intron_variant		1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.263+14_263+18delAAAAA		intron_variant		1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 64224 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11402 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 63 AN: 495297 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 145725

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000164

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000152

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.0000893

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 64224 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11402

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;