X-119837615-CAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chrX-119837615-C-CAAA
• rs34350340
• NM_080632.3:c.1302+139_1302+141dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_080632.3(UPF3B):​c.1302+139_1302+141dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 401,342 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 0 hem., cov: 16)
  • Exomes 𝑓: 0.00045 (0 hom. 0 hem.)
• Consequence: UPF3B NM_080632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000448 (160/357020) while in subpopulation MID AF= 0.000822 (1/1216). AF 95% confidence interval is 0.000378. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3B	NM_080632.3	c.1302+139_1302+141dupTTT		intron_variant	Intron 10 of 10	ENST00000276201.7	NP_542199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF3B	ENST00000276201.7	c.1302+141_1302+142insTTT		intron_variant	Intron 10 of 10	1	NM_080632.3	ENSP00000276201.3
UPF3B	ENST00000345865.6	c.1263+141_1263+142insTTT		intron_variant	Intron 9 of 9	1		ENSP00000245418.2

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 5 AN: 44312 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 7392

Gnomad AFR AF: 0.000206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00176

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000448 AC: 160 AN: 357020 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 107810

Gnomad4 AFR exome AF: 0.000549

Gnomad4 AMR exome AF: 0.000695

Gnomad4 ASJ exome AF: 0.000693

Gnomad4 EAS exome AF: 0.000371

Gnomad4 SAS exome AF: 0.000357

Gnomad4 FIN exome AF: 0.000482

Gnomad4 NFE exome AF: 0.000447

Gnomad4 OTH exome AF: 0.000266

GnomAD4 genome AF: 0.000113 AC: 5 AN: 44322 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 7398

Gnomad4 AFR AF: 0.000205

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00176

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs34350340; hg19: chrX-118971578;