rs761474818

Variant names:

• chr13-114282078-C-G
• rs761474818
• NM_023011.4:c.265C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-114282078-C-G
• chr13-114282078-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023011.4(UPF3A):​c.265C>G​(p.Arg89Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,427,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: UPF3A NM_023011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20294401).

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.265C>G	p.Arg89Gly	missense	Exon 2 of 10	NP_075387.1	Q9H1J1-1
	UPF3A	NM_080687.3		c.265C>G	p.Arg89Gly	missense	Exon 2 of 9	NP_542418.1	Q9H1J1-2
	UPF3A	NM_001353651.2		c.265C>G	p.Arg89Gly	missense	Exon 2 of 5	NP_001340580.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPF3A	ENST00000375299.8	TSL:1 MANE Select	c.265C>G	p.Arg89Gly	missense	Exon 2 of 10	ENSP00000364448.3	Q9H1J1-1
	UPF3A	ENST00000351487.5	TSL:1	c.265C>G	p.Arg89Gly	missense	Exon 2 of 9	ENSP00000329592.5	Q9H1J1-2
	UPF3A	ENST00000966313.1		c.265C>G	p.Arg89Gly	missense	Exon 2 of 11	ENSP00000636372.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427784 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 707394

African (AFR) AF: 0.00 AC: 0 AN: 32738

American (AMR) AF: 0.00 AC: 0 AN: 40300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25550

East Asian (EAS) AF: 0.00 AC: 0 AN: 37914

South Asian (SAS) AF: 0.00 AC: 0 AN: 82002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096178

Other (OTH) AF: 0.0000169 AC: 1 AN: 59070

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.90	N
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Benign	0.24	T
Sift4G	Benign	0.65	T
Polyphen		0.0030	B
Vest4		0.29
MutPred		0.46		Loss of stability (P = 0.0675)
MVP		0.49
MPC		0.23
ClinPred		0.68	D
GERP RS		4.8
PromoterAI		0.095	Neutral
Varity_R		0.34
gMVP		0.23
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs761474818; hg19: chr13-115047553;