Variant X-119837615-C-CA 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.1302+141dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 373,951 control chromosomes in the GnomAD database, including 360 homozygotes. There are 417 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 358 hom., 404 hem., cov: 16)

Exomes 𝑓: 0.066 ( 2 hom. 13 hem. )

Consequence

UPF3B
NM_080632.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74

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-119837615-C-CA is Benign according to our data. Variant chrX-119837615-C-CA is described in ClinVar as [Benign]. Clinvar id is 1229607.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3B	NM_080632.3 link	c.1302+141dupT		intron_variant	Intron 10 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.1302+141_1302+142insT		intron_variant	Intron 10 of 10	1	NM_080632.3	ENSP00000276201.3		Q9BZI7-1
UPF3B	ENST00000345865.6 link	c.1263+141_1263+142insT		intron_variant	Intron 9 of 9	1		ENSP00000245418.2		Q9BZI7-2

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

4977

AN:

43985

Hom.:

358

Cov.:

AF XY:

0.0549

AC XY:

403

AN XY:

7347

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.00837

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0312

Gnomad EAS

AF:

0.0239

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.0482

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.137

GnomAD4 exome

AF:

0.0660

AC:

21771

AN:

329957

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

83351

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.0680

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0695

Gnomad4 NFE exome

AF:

0.0661

Gnomad4 OTH exome

AF:

0.0724

GnomAD4 genome

AF:

0.113

AC:

4981

AN:

43994

Hom.:

358

Cov.:

AF XY:

0.0550

AC XY:

404

AN XY:

7352

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0312

Gnomad4 EAS

AF:

0.0240

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.0482

Gnomad4 NFE

AF:

0.0374

Gnomad4 OTH

AF:

0.135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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