Genetic Variant UPF3A:p.Ala17Glu (chr13-114281689-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023011.4(UPF3A):c.50C>A(p.Ala17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A17V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UPF3A
NM_023011.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

0 publications found

Variant links:

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]

UPF3A links:

ENSG00000289904 (HGNC:):

ENSG00000289904 links:

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ACMG classification

Classification was made for transcript

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=0.19092107).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UPF3A	NM_023011.4	MANE Select	c.50C>A	p.Ala17Glu	missense	Exon 1 of 10	NP_075387.1	Q9H1J1-1
UPF3A	NM_080687.3		c.50C>A	p.Ala17Glu	missense	Exon 1 of 9	NP_542418.1	Q9H1J1-2
UPF3A	NM_001353651.2		c.50C>A	p.Ala17Glu	missense	Exon 1 of 5	NP_001340580.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UPF3A	ENST00000375299.8	TSL:1 MANE Select	c.50C>A	p.Ala17Glu	missense	Exon 1 of 10	ENSP00000364448.3	Q9H1J1-1
UPF3A	ENST00000351487.5	TSL:1	c.50C>A	p.Ala17Glu	missense	Exon 1 of 9	ENSP00000329592.5	Q9H1J1-2
UPF3A	ENST00000966313.1		c.50C>A	p.Ala17Glu	missense	Exon 1 of 11	ENSP00000636372.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1386444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683060

African (AFR)

AF:

0.00

AC:

AN:

30424

American (AMR)

AF:

0.00

AC:

AN:

35734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24826

East Asian (EAS)

AF:

0.00

AC:

AN:

34980

South Asian (SAS)

AF:

0.00

AC:

AN:

78336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074620

Other (OTH)

AF:

0.00

AC:

AN:

57418

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.6

PhyloP100

-0.15

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.75

REVEL

Benign

0.19

Sift

Uncertain

0.0090

Sift4G

Benign

1.0

Polyphen

0.93

Vest4

0.15

MutPred

0.23

Gain of solvent accessibility (P = 0.005)

MVP

0.86

MPC

0.20

ClinPred

0.19

GERP RS

0.38

PromoterAI

0.029

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over