13-114281689-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023011.4(UPF3A):c.50C>T(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,538,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

UPF3A
NM_023011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.11285052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF3A	NM_023011.4 link	c.50C>T	p.Ala17Val	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>T	p.Ala17Val	missense_variant	Exon 1 of 10	1	NM_023011.4	ENSP00000364448.3		Q9H1J1-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000357

AC:

AN:

140216

Hom.:

AF XY:

0.0000261

AC XY:

AN XY:

76520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000790

Gnomad NFE exome

AF:

0.0000760

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000577

AC:

AN:

1386444

Hom.:

Cov.:

AF XY:

0.0000498

AC XY:

AN XY:

683060

show subpopulations

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:

0.0000128

Gnomad4 FIN exome

AF:

0.0000446

Gnomad4 NFE exome

AF:

0.0000698

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000793

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50C>T (p.A17V) alteration is located in exon 1 (coding exon 1) of the UPF3A gene. This alteration results from a C to T substitution at nucleotide position 50, causing the alanine (A) at amino acid position 17 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0038

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.67

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;.;L

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.90

N;.;N

REVEL

Benign

0.051

Sift

Uncertain

0.015

D;.;D

Sift4G

Benign

0.36

T;T;T

Polyphen

0.10

B;.;B

Vest4

0.11

MutPred

0.32

Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);

MVP

0.75

MPC

0.20

ClinPred

0.047

GERP RS

0.38

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.049

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over