dbSNP rs920206864: UPF3A:p.Ala17Glu (chr13-114281689-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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:

LOC105370384 (HGNC:):

LOC105370384 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19092107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3A	NM_023011.4 link	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 10	ENST00000375299.8	NP_075387.1	Q9H1J1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF3A	ENST00000375299.8 link	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 10	1	NM_023011.4	ENSP00000364448.3		Q9H1J1-1

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0019

T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.69

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.6

L;.;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.75

N;.;N

REVEL

Benign

0.19

Sift

Uncertain

0.0090

D;.;D

Sift4G

Benign

1.0

T;T;T

Polyphen

0.93

P;.;D

Vest4

0.15

MutPred

0.23

Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);

MVP

0.86

MPC

0.20

ClinPred

0.19

GERP RS

0.38

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over