X-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTT

Position:

• chrX-119851748-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_080632.3(UPF3B):​c.263+18_263+19insAAAAAAAAAAAAAAAAAAAAAA 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 0.0019 (18 hom., 5 hem., cov: 0)
  • Exomes 𝑓: 0.00025 (2 hom. 22 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0650

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-119851748-C-CTTTTTTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chrX-119851748-C-CTTTTTTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2046329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00187 (120/64199) while in subpopulation AFR AF= 0.00834 (106/12710). AF 95% confidence interval is 0.00705. There are 18 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.263+18_263+19insAAAAAAAAAAAAAAAAAAAAAA		intron_variant		ENST00000276201.7	NP_542199.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 120 AN: 64207 Hom.: 18 Cov.: 0 AF XY: 0.000438 AC XY: 5 AN XY: 11403

Gnomad AFR AF: 0.00834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000454

Gnomad ASJ AF: 0.00350

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000252

Gnomad OTH AF: 0.00515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000248 AC: 123 AN: 495777 Hom.: 2 Cov.: 0 AF XY: 0.000151 AC XY: 22 AN XY: 146019

Gnomad4 AFR exome AF: 0.00254

Gnomad4 AMR exome AF: 0.000985

Gnomad4 ASJ exome AF: 0.000525

Gnomad4 EAS exome AF: 0.000664

Gnomad4 SAS exome AF: 0.000869

Gnomad4 FIN exome AF: 0.0000379

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.000223

GnomAD4 genome AF: 0.00187 AC: 120 AN: 64199 Hom.: 18 Cov.: 0 AF XY: 0.000439 AC XY: 5 AN XY: 11401

Gnomad4 AFR AF: 0.00834

Gnomad4 AMR AF: 0.000453

Gnomad4 ASJ AF: 0.00350

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000252

Gnomad4 OTH AF: 0.00509

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic X-linked intellectual disability 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55712755; hg19: chrX-118985711;