X-119851748-CTTTTT-CTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_080632.3(UPF3B):​c.263+13_263+18dupAAAAAA 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 0.013 (75 hom., 176 hem., cov: 0)
  • Exomes 𝑓: 0.0023 (12 hom. 42 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant X-119851748-C-CTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1635780.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.263+13_263+18dupAAAAAA		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+19insAAAAAA		intron_variant		1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.263+18_263+19insAAAAAA		intron_variant		1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 846 AN: 64226 Hom.: 75 Cov.: 0 AF XY: 0.0153 AC XY: 174 AN XY: 11402

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00634

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0123

Gnomad NFE AF: 0.000277

Gnomad OTH AF: 0.0116

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00226 AC: 1113 AN: 492481 Hom.: 12 Cov.: 0 AF XY: 0.000292 AC XY: 42 AN XY: 143905

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.0123

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.000761

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.00410

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0132 AC: 849 AN: 64218 Hom.: 75 Cov.: 0 AF XY: 0.0154 AC XY: 176 AN XY: 11400

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00139

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000277

Gnomad4 OTH AF: 0.0114

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

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;