X-119837615-CAAAAAAAAAAA-CAAAAAAAAA

Variant names:

• chrX-119837615-CAA-C
• rs34350340
• NM_080632.3:c.1302+140_1302+141delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_080632.3(UPF3B):​c.1302+140_1302+141delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 362,801 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0037 (0 hom., 18 hem., cov: 16)
  • Exomes 𝑓: 0.054 (0 hom. 1 hem.)
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.1302+140_1302+141delTT		intron_variant	Intron 10 of 10	ENST00000276201.7	NP_542199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7	c.1302+140_1302+141delTT		intron_variant	Intron 10 of 10	1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.1263+140_1263+141delTT		intron_variant	Intron 9 of 9	1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 164 AN: 44292 Hom.: 0 Cov.: 16 AF XY: 0.00244 AC XY: 18 AN XY: 7388

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00169

GnomAD4 exome AF: 0.0540 AC: 17202 AN: 318499 Hom.: 0 AF XY: 0.0000116 AC XY: 1 AN XY: 86237

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.0585

Gnomad4 ASJ exome AF: 0.0561

Gnomad4 EAS exome AF: 0.0592

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.0677

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.00370 AC: 164 AN: 44302 Hom.: 0 Cov.: 16 AF XY: 0.00243 AC XY: 18 AN XY: 7394

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.00146

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34350340; hg19: chrX-118971578;