X-119851748-CTTTTTTT-CTTTTTT

Variant names:

• chrX-119851748-CT-C
• rs55712755
• NM_080632.3:c.263+18delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.34 (3150 hom., 4973 hem., cov: 0)
  • Exomes 𝑓: 0.32 (2401 hom. 5605 hem.)
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

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]

UPF3B Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability 14

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability with marfanoid habitus

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant X-119851748-CT-C is Benign according to our data. Variant chrX-119851748-CT-C is described in ClinVar as [Benign]. Clinvar id is 1599904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.263+18delA		intron_variant	Intron 2 of 10	ENST00000276201.7	NP_542199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7	c.263+18delA		intron_variant	Intron 2 of 10	1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.263+18delA		intron_variant	Intron 2 of 9	1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 22211 AN: 64371 Hom.: 3153 Cov.: 0

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.530

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.320 AC: 132816 AN: 414455 Hom.: 2401 Cov.: 0 AF XY: 0.0839 AC XY: 5605 AN XY: 66789

African (AFR) AF: 0.0584 AC: 425 AN: 7273

American (AMR) AF: 0.166 AC: 1847 AN: 11136

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 2981 AN: 9389

East Asian (EAS) AF: 0.0505 AC: 743 AN: 14722

South Asian (SAS) AF: 0.175 AC: 3840 AN: 21929

European-Finnish (FIN) AF: 0.317 AC: 7008 AN: 22097

Middle Eastern (MID) AF: 0.331 AC: 428 AN: 1293

European-Non Finnish (NFE) AF: 0.357 AC: 109820 AN: 307407

Other (OTH) AF: 0.298 AC: 5724 AN: 19209

GnomAD4 genome AF: 0.345 AC: 22201 AN: 64361 Hom.: 3150 Cov.: 0 AF XY: 0.439 AC XY: 4973 AN XY: 11333

African (AFR) AF: 0.0873 AC: 1112 AN: 12733

American (AMR) AF: 0.346 AC: 1530 AN: 4428

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 808 AN: 1999

East Asian (EAS) AF: 0.112 AC: 162 AN: 1445

South Asian (SAS) AF: 0.516 AC: 504 AN: 977

European-Finnish (FIN) AF: 0.578 AC: 883 AN: 1528

Middle Eastern (MID) AF: 0.532 AC: 41 AN: 77

European-Non Finnish (NFE) AF: 0.416 AC: 16592 AN: 39841

Other (OTH) AF: 0.355 AC: 281 AN: 792

Alfa AF: 0.224 Hom.: 585

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic X-linked intellectual disability 14 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55712755; hg19: chrX-118985711;