Genetic Variant NM_080632.3:c.264-34G>A (chrX-119851635-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_080632.3(UPF3B):c.264-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 19401 hom., 21195 hem., cov: 21)

Exomes 𝑓: 0.58 ( 118123 hom. 169250 hem. )

Failed GnomAD Quality Control

Consequence

UPF3B
NM_080632.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.545

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-119851635-C-T is Benign according to our data. Variant chrX-119851635-C-T is described in ClinVar as [Benign]. Clinvar id is 670475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3B	NM_080632.3 link	c.264-34G>A		intron_variant	Intron 2 of 10	ENST00000276201.7	NP_542199.1	Q9BZI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7 link	c.264-34G>A		intron_variant	Intron 2 of 10	1	NM_080632.3	ENSP00000276201.3		Q9BZI7-1
UPF3B	ENST00000345865.6 link	c.264-34G>A		intron_variant	Intron 2 of 9	1		ENSP00000245418.2		Q9BZI7-2

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

74260

AN:

109182

Hom.:

19407

Cov.:

AF XY:

0.671

AC XY:

21146

AN XY:

31494

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.710

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.682

GnomAD3 exomes

AF:

0.658

AC:

114572

AN:

174209

Hom.:

26883

AF XY:

0.643

AC XY:

38512

AN XY:

59887

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.826

Gnomad ASJ exome

AF:

0.574

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.676

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.583

AC:

562653

AN:

964815

Hom.:

118123

Cov.:

AF XY:

0.601

AC XY:

169250

AN XY:

281509

show subpopulations

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.824

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.950

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.508

Gnomad4 NFE exome

AF:

0.541

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.680

AC:

74301

AN:

109224

Hom.:

19401

Cov.:

AF XY:

0.672

AC XY:

21195

AN XY:

31546

show subpopulations

Gnomad4 AFR

AF:

0.926

Gnomad4 AMR

AF:

0.762

Gnomad4 ASJ

AF:

0.587

Gnomad4 EAS

AF:

0.945

Gnomad4 SAS

AF:

0.672

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.679

Alfa

AF:

0.624

Hom.:

9173

Bravo

AF:

0.720

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Syndromic X-linked intellectual disability 14

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.4

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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