Variant 3-52690984-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014366.5(GNL3):c.694G>A(p.Glu232Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,613,710 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 0 hom. )

Consequence

GNL3
NM_014366.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

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 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=0.016652554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GNL3	NM_014366.5 linkuse as main transcript	c.694G>A	p.Glu232Lys	missense_variant	8/15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/15		NP_996561.1
GNL3	NM_206826.1 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6 linkuse as main transcript	c.694G>A	p.Glu232Lys	missense_variant	8/15	1	NM_014366.5	ENSP00000395772	P2	Q9BVP2-1
GNL3	ENST00000394799.6 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/15	2		ENSP00000378278	A2	Q9BVP2-2
GNL3	ENST00000484022.1 linkuse as main transcript	n.435G>A		non_coding_transcript_exon_variant	3/5	2
GNL3	ENST00000496254.5 linkuse as main transcript	n.978G>A		non_coding_transcript_exon_variant	7/14	5

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000282

AC:

AN:

251478

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

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:

0.000598

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000620

AC:

906

AN:

1461488

Hom.:

Cov.:

AF XY:

0.000611

AC XY:

444

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000781

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000401

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000716

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000533

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

Aug 12, 2021

The c.694G>A (p.E232K) alteration is located in exon 8 (coding exon 8) of the GNL3 gene. This alteration results from a G to A substitution at nucleotide position 694, causing the glutamic acid (E) at amino acid position 232 to be replaced by a lysine (K). 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

0.074

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.50

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.036

Sift

Benign

0.90

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;.

Vest4

0.15

MVP

0.21

MPC

0.11

ClinPred

0.019

GERP RS

-1.6

Varity_R

0.030

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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