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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_080632.3(UPF3B):c.263+7_263+18dupAAAAAAAAAAAA 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 0.016 ( 93 hom., 182 hem., cov: 0)

Exomes 𝑓: 0.025 ( 144 hom. 1343 hem. )

Failed GnomAD Quality Control

Consequence

UPF3B
NM_080632.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-119851748-C-CTTTTTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 212547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0164 (1049/64143) while in subpopulation AFR AF= 0.0379 (481/12688). AF 95% confidence interval is 0.0351. There are 93 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 93 XL gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

1048

AN:

64151

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

182

AN XY:

11399

show subpopulations

Gnomad AFR

AF:

0.0380

Gnomad AMI

AF:

0.00562

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.00499

Gnomad EAS

AF:

0.0132

Gnomad SAS

AF:

0.0113

Gnomad FIN

AF:

0.00262

Gnomad MID

AF:

0.0247

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0283

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0252

AC:

11807

AN:

468932

Hom.:

144

Cov.:

AF XY:

0.00994

AC XY:

1343

AN XY:

135060

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.0611

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.0761

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0164

AC:

1049

AN:

64143

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

182

AN XY:

11397

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00499

Gnomad4 EAS

AF:

0.0132

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.00262

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0280

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Feb 01, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 25, 2013

- -

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