Variant rs11177 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014366.5(GNL3):c.116G>A(p.Arg39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,610,504 control chromosomes in the GnomAD database, including 118,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9707 hom., cov: 32)

Exomes 𝑓: 0.38 ( 108313 hom. )

Consequence

GNL3
NM_014366.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

GNL3 (HGNC:29931): (G protein nucleolar 3) The protein encoded by this gene may interact with p53 and may be involved in tumorigenesis. The encoded protein also appears to be important for stem cell proliferation. This protein is found in both the nucleus and nucleolus. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

GNL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014968812).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNL3	NM_014366.5 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	3/15	ENST00000418458.6
GNL3	NM_206825.2 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	3/15
GNL3	NM_206826.1 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	3/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNL3	ENST00000418458.6 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	3/15	1	NM_014366.5	P2	Q9BVP2-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51406

AN:

151914

Hom.:

9702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.384

AC:

96246

AN:

250782

Hom.:

19845

AF XY:

0.374

AC XY:

50794

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.379

AC:

553164

AN:

1458472

Hom.:

108313

Cov.:

AF XY:

0.374

AC XY:

271616

AN XY:

725790

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.338

AC:

51434

AN:

152032

Hom.:

9707

Cov.:

AF XY:

0.340

AC XY:

25288

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.389

Hom.:

29495

Bravo

AF:

0.339

TwinsUK

AF:

0.375

AC:

1392

ALSPAC

AF:

0.384

AC:

1480

ESP6500AA

AF:

0.173

AC:

761

ESP6500EA

AF:

0.403

AC:

3465

ExAC

AF:

0.373

AC:

45341

Asia WGS

AF:

0.330

AC:

1147

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;T;D;D

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

.;L;.;.

MutationTaster

Benign

0.69

P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.064

.;B;.;.

Vest4

0.051, 0.082

MPC

0.15

ClinPred

0.0091

GERP RS

1.9

Varity_R

0.090

gMVP

0.064

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over