3-52693805-G-A

Position:

chr3-52693805-G-A

Variant summary

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

The NM_014366.5(GNL3):c.1498G>A(p.Asp500Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GNL3
NM_014366.5 missense, splice_region

Scores

Splicing: ADA: 0.00008461

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.735

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:

GNL3 (HGNC:):

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=0.053819984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNL3	NM_014366.5 linkuse as main transcript	c.1498G>A	p.Asp500Asn	missense_variant, splice_region_variant	13/15	ENST00000418458.6	NP_055181.3	Q9BVP2-1
GNL3	NM_206825.2 linkuse as main transcript	c.1462G>A	p.Asp488Asn	missense_variant, splice_region_variant	13/15		NP_996561.1	Q9BVP2-2
GNL3	NM_206826.1 linkuse as main transcript	c.1462G>A	p.Asp488Asn	missense_variant, splice_region_variant	13/15		NP_996562.1	Q9BVP2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GNL3	ENST00000418458.6 linkuse as main transcript	c.1498G>A	p.Asp500Asn	missense_variant, splice_region_variant	13/15	1	NM_014366.5	ENSP00000395772.1	Q9BVP2-1
GNL3	ENST00000394799.6 linkuse as main transcript	c.1462G>A	p.Asp488Asn	missense_variant, splice_region_variant	13/15	2		ENSP00000378278.2	Q9BVP2-2
GNL3	ENST00000496254.5 linkuse as main transcript	n.1782G>A		splice_region_variant, non_coding_transcript_exon_variant	12/14	5
GNL3	ENST00000497356.1 linkuse as main transcript	n.*26G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459438

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

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

Jul 05, 2023

The c.1498G>A (p.D500N) alteration is located in exon 13 (coding exon 13) of the GNL3 gene. This alteration results from a G to A substitution at nucleotide position 1498, causing the aspartic acid (D) at amino acid position 500 to be replaced by an asparagine (N). 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

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

DANN

Benign

0.89

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.35

N;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.040

Sift

Benign

0.46

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0

B;.

Vest4

0.081

MVP

0.20

MPC

0.097

ClinPred

0.036

GERP RS

-1.0

Varity_R

0.028

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.030

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