rs763045306

Variant names:

• chr4-2939621-C-A
• rs763045306
• NM_001291978.2:c.2224G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-2939621-C-A
• chr4-2939621-C-G
• chr4-2939621-C-T

Variant summary

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

The NM_001291978.2(NOP14):​c.2224G>T​(p.Glu742*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOP14 NM_001291978.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

Genes affected

NOP14 (HGNC:16821): (NOP14 nucleolar protein) This gene encodes a protein that plays a role in pre-18s rRNA processing and small ribosomal subunit assembly. The encoded protein may be involved in the regulation of pancreatic cancer cell proliferation and migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

NOP14-AS1 (HGNC:20205): (NOP14 antisense RNA 1)

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
NOP14	NM_001291978.2	c.2224G>T	p.Glu742*	stop_gained	Exon 16 of 18	ENST00000416614.7	NP_001278907.1
NOP14	NM_003703.3	c.2224G>T	p.Glu742*	stop_gained	Exon 16 of 19		NP_003694.1
NOP14	NM_001291979.2	c.2224G>T	p.Glu742*	stop_gained	Exon 16 of 17		NP_001278908.1
NOP14-AS1	NR_015453.2	n.2697+829C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7	c.2224G>T	p.Glu742*	stop_gained	Exon 16 of 18	1	NM_001291978.2	ENSP00000405068.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.59	D
Vest4		0.26
GERP RS		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs763045306; hg19: chr4-2941348;