Variant 4-2939594-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001291978.2(NOP14):c.2251C>T(p.Arg751Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,920 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 (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

NOP14
NM_001291978.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.771

Variant links:

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 links:

NOP14-AS1 (HGNC:):

NOP14-AS1 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=0.14312524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2 linkuse as main transcript	c.2251C>T	p.Arg751Trp	missense_variant	16/18	ENST00000416614.7	NP_001278907.1	P78316-1A8KA74
NOP14	NM_003703.3 linkuse as main transcript	c.2251C>T	p.Arg751Trp	missense_variant	16/19		NP_003694.1	P78316-1A8KA74
NOP14	NM_001291979.2 linkuse as main transcript	c.2251C>T	p.Arg751Trp	missense_variant	16/17		NP_001278908.1	P78316-2A8KA74
NOP14-AS1	NR_015453.2 linkuse as main transcript	n.2697+802G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7 linkuse as main transcript	c.2251C>T	p.Arg751Trp	missense_variant	16/18	1	NM_001291978.2	ENSP00000405068.2		P78316-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251302

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

183

AN:

1461594

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000360

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.2251C>T (p.R751W) alteration is located in exon 16 (coding exon 16) of the NOP14 gene. This alteration results from a C to T substitution at nucleotide position 2251, causing the arginine (R) at amino acid position 751 to be replaced by a tryptophan (W). 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

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.69

.;T;T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.2

M;M;.;M

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.26

MVP

0.55

MPC

0.084

ClinPred

0.15

GERP RS

6.0

Varity_R

0.14

gMVP

0.34

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