Variant X-119851748-CTTTTT-CTTTTTTTTTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_080632.3(UPF3B):c.263+11_263+18dupAAAAAAAA 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 0.030 ( 127 hom., 334 hem., cov: 0)

Exomes 𝑓: 0.010 ( 102 hom. 383 hem. )

Failed GnomAD Quality Control

Consequence

UPF3B
NM_080632.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0650

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-119851748-C-CTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1594434.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPF3B	NM_080632.3 link	c.263+11_263+18dupAAAAAAAA		intron_variant		ENST00000276201.7	NP_542199.1	Q9BZI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7 link	c.263+18_263+19insAAAAAAAA		intron_variant		1	NM_080632.3	ENSP00000276201.3		Q9BZI7-1
UPF3B	ENST00000345865.6 link	c.263+18_263+19insAAAAAAAA		intron_variant		1		ENSP00000245418.2		Q9BZI7-2

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

1927

AN:

64116

Hom.:

127

Cov.:

AF XY:

0.0293

AC XY:

334

AN XY:

11400

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0506

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0669

Gnomad FIN

AF:

0.00524

Gnomad MID

AF:

0.0370

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0398

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0102

AC:

4940

AN:

485605

Hom.:

102

Cov.:

AF XY:

0.00273

AC XY:

383

AN XY:

140405

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.0565

Gnomad4 SAS exome

AF:

0.0171

Gnomad4 FIN exome

AF:

0.00634

Gnomad4 NFE exome

AF:

0.00733

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0301

AC:

1927

AN:

64108

Hom.:

127

Cov.:

AF XY:

0.0293

AC XY:

334

AN XY:

11398

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.0506

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0666

Gnomad4 FIN

AF:

0.00524

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0406

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability 14

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over