rs149711534

Variant names:

• chr19-18846006-C-G
• rs149711534
• NM_002911.4:c.258C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18846006-C-G
• chr19-18846006-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002911.4(UPF1):​c.258C>G​(p.Asn86Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N86N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPF1 NM_002911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF1	NM_002911.4	c.258C>G	p.Asn86Lys	missense_variant	Exon 2 of 24	ENST00000262803.10	NP_002902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF1	ENST00000262803.10	c.258C>G	p.Asn86Lys	missense_variant	Exon 2 of 24	1	NM_002911.4	ENSP00000262803.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	-0.046	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.92	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.11	T;.
Sift4G	Benign	0.40	T;T
Polyphen		1.0	D;D
Vest4		0.86
MutPred		0.40		Gain of ubiquitination at N86 (P = 0.0048);Gain of ubiquitination at N86 (P = 0.0048);
MVP		0.69
MPC		1.4
ClinPred		0.63	D
GERP RS		-2.6
Varity_R		0.33
gMVP		0.48

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

Other links and lift over

dbSNP: rs149711534; hg19: chr19-18956815;