Variant rs2289247 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.1099G>A(p.Val367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,612,612 control chromosomes in the GnomAD database, including 144,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.46 ( 16078 hom., cov: 31)

Exomes 𝑓: 0.42 ( 128470 hom. )

Consequence

GNL3
NM_014366.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.172

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6167334E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GNL3	NM_014366.5 linkuse as main transcript	c.1099G>A	p.Val367Met	missense_variant	11/15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2 linkuse as main transcript	c.1063G>A	p.Val355Met	missense_variant	11/15		NP_996561.1
GNL3	NM_206826.1 linkuse as main transcript	c.1063G>A	p.Val355Met	missense_variant	11/15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6 linkuse as main transcript	c.1099G>A	p.Val367Met	missense_variant	11/15	1	NM_014366.5	ENSP00000395772	P2	Q9BVP2-1
GNL3	ENST00000394799.6 linkuse as main transcript	c.1063G>A	p.Val355Met	missense_variant	11/15	2		ENSP00000378278	A2	Q9BVP2-2
GNL3	ENST00000496254.5 linkuse as main transcript	n.1383G>A		non_coding_transcript_exon_variant	10/14	5
GNL3	ENST00000497356.1 linkuse as main transcript	n.72G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69054

AN:

151684

Hom.:

16058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.432

AC:

108345

AN:

250910

Hom.:

24250

AF XY:

0.418

AC XY:

56743

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.416

AC:

607442

AN:

1460810

Hom.:

128470

Cov.:

AF XY:

0.410

AC XY:

298284

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.455

AC:

69129

AN:

151802

Hom.:

16078

Cov.:

AF XY:

0.454

AC XY:

33705

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.430

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.431

Hom.:

37778

Bravo

AF:

0.470

TwinsUK

AF:

0.399

AC:

1479

ALSPAC

AF:

0.407

AC:

1570

ESP6500AA

AF:

0.518

AC:

2282

ESP6500EA

AF:

0.431

AC:

3704

ExAC

AF:

0.429

AC:

52084

Asia WGS

AF:

0.378

AC:

1315

AN:

3478

EpiCase

AF:

0.431

EpiControl

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.031

T;T

MetaRNN

Benign

0.000026

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.84

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

0.97

N;N

REVEL

Benign

0.039

Sift

Benign

0.38

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0

B;.

Vest4

0.027

MPC

0.10

ClinPred

0.0043

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.20

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

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