dbSNP rs1342113393: UPF1:p.Gly64Asp (chr19-18832400-G-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_002911.4(UPF1):c.191G>A(p.Gly64Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000466 in 859,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000047 ( 0 hom. )

Consequence

UPF1
NM_002911.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

UPF1 (HGNC:9962): (UPF1 RNA helicase and ATPase) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. 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 is located only in the cytoplasm. When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

UPF1 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=0.20067927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF1	NM_002911.4 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 1 of 24	ENST00000262803.10	NP_002902.2	Q92900-2A0A024R7L5
UPF1	NM_001297549.2 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 1 of 24		NP_001284478.1	Q92900-1A0A024R7L8B3KY55
UPF1	XM_017027105.3 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 1 of 24		XP_016882594.1
UPF1	XM_017027106.3 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 1 of 24		XP_016882595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF1	ENST00000262803.10 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 1 of 24	1	NM_002911.4	ENSP00000262803.5		Q92900-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000466

AC:

AN:

859114

Hom.:

Cov.:

AF XY:

0.00000752

AC XY:

AN XY:

399148

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000514

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.077

.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.57

T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.53

N;.

REVEL

Benign

0.28

Sift

Benign

0.59

T;.

Sift4G

Benign

0.60

T;T

Polyphen

0.0

B;B

Vest4

0.19

MutPred

0.19

Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);

MVP

0.47

MPC

1.5

ClinPred

0.17

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.15

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over