4-2941647-T-C

Position:

chr4-2941647-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001291978.2(NOP14):c.2134A>G(p.Met712Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NOP14
NM_001291978.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.08

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.094567895).

BP6

Variant 4-2941647-T-C is Benign according to our data. Variant chr4-2941647-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2279513.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2 linkuse as main transcript	c.2134A>G	p.Met712Val	missense_variant	15/18	ENST00000416614.7	NP_001278907.1	P78316-1A8KA74
NOP14	NM_003703.3 linkuse as main transcript	c.2134A>G	p.Met712Val	missense_variant	15/19		NP_003694.1	P78316-1A8KA74
NOP14	NM_001291979.2 linkuse as main transcript	c.2134A>G	p.Met712Val	missense_variant	15/17		NP_001278908.1	P78316-2A8KA74
NOP14-AS1	NR_015453.2 linkuse as main transcript	n.2697+2855T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7 linkuse as main transcript	c.2134A>G	p.Met712Val	missense_variant	15/18	1	NM_001291978.2	ENSP00000405068.2		P78316-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248462

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134602

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461206

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0010

DANN

Benign

0.37

DEOGEN2

Benign

0.0049

T;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.14

.;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.075

N;N;.;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.51

N;N;N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.050

MutPred

0.68

Loss of stability (P = 0.4024);Loss of stability (P = 0.4024);Loss of stability (P = 0.4024);Loss of stability (P = 0.4024);

MVP

0.061

MPC

0.076

ClinPred

0.037

GERP RS

-11

Varity_R

0.039

gMVP

0.42

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