13-114281707-GG-AA

Variant names:

• chr13-114281707-GG-AA
• NM_023011.4:c.68_69delGGinsAA
• UPF3A p.Arg23Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_023011.4(UPF3A):​c.68_69delGGinsAA​(p.Arg23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPF3A NM_023011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 0 publications found

Genes affected

UPF3A (HGNC:20332): (UPF3A 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 13. Several splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ENSG00000289904 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPF3A	NM_023011.4	MANE Select	c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	NP_075387.1	Q9H1J1-1
	UPF3A	NM_080687.3		c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	NP_542418.1	Q9H1J1-2
	UPF3A	NM_001353651.2		c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	NP_001340580.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPF3A	ENST00000375299.8	TSL:1 MANE Select	c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	ENSP00000364448.3	Q9H1J1-1
	UPF3A	ENST00000351487.5	TSL:1	c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	ENSP00000329592.5	Q9H1J1-2
	UPF3A	ENST00000966313.1		c.68_69delGGinsAA	p.Arg23Lys	missense	N/A	ENSP00000636372.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-115047182;