4-2939600-G-A

Position:

chr4-2939600-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001291978.2(NOP14):c.2245C>T(p.Leu749Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,613,936 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 4 hom. )

Consequence

NOP14
NM_001291978.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.99

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005493492).

BP6

Variant 4-2939600-G-A is Benign according to our data. Variant chr4-2939600-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2399796.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2 linkuse as main transcript	c.2245C>T	p.Leu749Phe	missense_variant	16/18	ENST00000416614.7	NP_001278907.1	P78316-1A8KA74
NOP14	NM_003703.3 linkuse as main transcript	c.2245C>T	p.Leu749Phe	missense_variant	16/19		NP_003694.1	P78316-1A8KA74
NOP14	NM_001291979.2 linkuse as main transcript	c.2245C>T	p.Leu749Phe	missense_variant	16/17		NP_001278908.1	P78316-2A8KA74
NOP14-AS1	NR_015453.2 linkuse as main transcript	n.2697+808G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7 linkuse as main transcript	c.2245C>T	p.Leu749Phe	missense_variant	16/18	1	NM_001291978.2	ENSP00000405068.2		P78316-1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000903

AC:

227

AN:

251322

Hom.:

AF XY:

0.000861

AC XY:

117

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00315

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000671

AC:

980

AN:

1461570

Hom.:

Cov.:

AF XY:

0.000684

AC XY:

497

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000536

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152366

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000589

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.2245C>T (p.L749F) 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 2245, causing the leucine (L) at amino acid position 749 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

NOP14: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.7

DANN

Benign

0.75

DEOGEN2

Benign

0.0062

T;T;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.62

.;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.70

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.53

P;P;P;.

Vest4

0.20

MVP

0.25

MPC

0.25

ClinPred

0.013

GERP RS

-0.49

Varity_R

0.047

gMVP

0.10

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