X-119851748-CTTTTT-CTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTT

Variant summary

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

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (52 hom., 176 hem., cov: 0)
  • Exomes 𝑓: 0.0016 (9 hom. 23 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: 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-CTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTT is described in ClinVar as [Benign]. Clinvar id is 2039555.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF3B	NM_080632.3	c.263+18_263+19insAAAAA		intron_variant		ENST00000276201.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF3B	ENST00000276201.7	c.263+18_263+19insAAAAA		intron_variant		1	NM_080632.3	A1
UPF3B	ENST00000345865.6	c.263+18_263+19insAAAAA		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 813 AN: 64215 Hom.: 52 Cov.: 0 AF XY: 0.0153 AC XY: 174 AN XY: 11403

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00454

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000694

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000352

Gnomad OTH AF: 0.00642

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00157 AC: 777 AN: 493981 Hom.: 9 Cov.: 0 AF XY: 0.000159 AC XY: 23 AN XY: 144775

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.000439

Gnomad4 EAS exome AF: 0.00527

Gnomad4 SAS exome AF: 0.000839

Gnomad4 FIN exome AF: 0.000190

Gnomad4 NFE exome AF: 0.000592

Gnomad4 OTH exome AF: 0.00319

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0127 AC: 814 AN: 64207 Hom.: 52 Cov.: 0 AF XY: 0.0154 AC XY: 176 AN XY: 11401

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.00453

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000696

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000352

Gnomad4 OTH AF: 0.00635

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic X-linked intellectual disability 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

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;