4-2939339-C-T

Variant names:

• chr4-2939339-C-T
• rs145832505
• NM_001291978.2:c.2323G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001291978.2(NOP14):​c.2323G>A​(p.Glu775Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000196 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E775Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: NOP14 NM_001291978.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30424243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291978.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP14	NM_001291978.2	MANE Select	c.2323G>A	p.Glu775Lys	missense	Exon 17 of 18	NP_001278907.1	P78316-1
	NOP14	NM_003703.3		c.2323G>A	p.Glu775Lys	missense	Exon 17 of 19	NP_003694.1	P78316-1
	NOP14	NM_001291979.2		c.2306+200G>A		intron	N/A	NP_001278908.1	P78316-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP14	ENST00000416614.7	TSL:1 MANE Select	c.2323G>A	p.Glu775Lys	missense	Exon 17 of 18	ENSP00000405068.2	P78316-1
	NOP14	ENST00000314262.10	TSL:1	c.2323G>A	p.Glu775Lys	missense	Exon 17 of 19	ENSP00000315674.6	P78316-1
	NOP14	ENST00000398071.4	TSL:1	c.2306+200G>A		intron	N/A	ENSP00000381146.4	P78316-2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000263 AC: 66 AN: 251280 AF XY: 0.000265

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000202 AC: 295 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.000216 AC XY: 157 AN XY: 727134

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000447 AC: 20 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 55 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000180 AC: 200 AN: 1111990

Other (OTH) AF: 0.000298 AC: 18 AN: 60390

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74466

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000383 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.21
Sift	Uncertain	0.014	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.64
MVP		0.65
MPC		0.44
ClinPred		0.40	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.34
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs145832505; hg19: chr4-2941066; COSMIC: COSV58624248; COSMIC: COSV58624248;