chr3-52687289-G-A

Position:

• chr3-52687289-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418458.6(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 ENST00000418458.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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]

ACMG classification

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	Protein	UniProt
GNL3	NM_014366.5	c.116G>A	p.Arg39Gln	missense_variant	3/15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2	c.80G>A	p.Arg27Gln	missense_variant	3/15		NP_996561.1
GNL3	NM_206826.1	c.80G>A	p.Arg27Gln	missense_variant	3/15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.116G>A	p.Arg39Gln	missense_variant	3/15	1	NM_014366.5	ENSP00000395772	P2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51406 AN: 151914 Hom.: 9702 Cov.: 32

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

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.: 32 AF XY: 0.374 AC XY: 271616 AN XY: 725790

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.: 32 AF XY: 0.340 AC XY: 25288 AN XY: 74308

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	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
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	D
LIST_S2	Uncertain	0.89	D;T;D;D
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	.;L;.;.
MutationTaster	Benign	0.69	P;P
PrimateAI	Benign	0.37	T
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	T
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

Other links and lift over

dbSNP: rs11177; hg19: chr3-52721305; COSMIC: COSV66920847; COSMIC: COSV66920847;