X-119837615-CA-C

Variant summary

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

The NM_080632.3(UPF3B):c.1302+141del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 345,500 control chromosomes in the GnomAD database, including 148 homozygotes. There are 300 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (143 hom., 243 hem., cov: 16)
  • Exomes 𝑓: 0.19 (5 hom. 57 hem.)
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant X-119837615-CA-C is Benign according to our data. Variant chrX-119837615-CA-C is described in ClinVar as [Benign]. Clinvar id is 1259359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF3B	NM_080632.3	c.1302+141del		intron_variant		ENST00000276201.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF3B	ENST00000276201.7	c.1302+141del		intron_variant		1	NM_080632.3	A1
UPF3B	ENST00000345865.6	c.1263+141del		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 3825 AN: 44282 Hom.: 142 Cov.: 16 AF XY: 0.0329 AC XY: 242 AN XY: 7362

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0415

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.190 AC: 57150 AN: 301208 Hom.: 5 AF XY: 0.000987 AC XY: 57 AN XY: 57770

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.0864 AC: 3826 AN: 44292 Hom.: 143 Cov.: 16 AF XY: 0.0330 AC XY: 243 AN XY: 7368

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.0161

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0705

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

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;