rs11177

Variant names:

• chr3-52687289-G-A
• rs11177
• NM_014366.5:c.116G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-52687289-G-A
• chr3-52687289-G-C
• chr3-52687289-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9707 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108313 hom.)
• Consequence: GNL3 NM_014366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 115 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GNL3	NM_014366.5	c.116G>A	p.Arg39Gln	missense_variant	Exon 3 of 15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2	c.80G>A	p.Arg27Gln	missense_variant	Exon 3 of 15		NP_996561.1
GNL3	NM_206826.1	c.80G>A	p.Arg27Gln	missense_variant	Exon 3 of 15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.116G>A	p.Arg39Gln	missense_variant	Exon 3 of 15	1	NM_014366.5	ENSP00000395772.1

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

GnomAD2 exomes AF: 0.384 AC: 96246 AN: 250782 AF XY: 0.374

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 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

African (AFR) AF: 0.165 AC: 5524 AN: 33444

American (AMR) AF: 0.517 AC: 23085 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12015 AN: 26100

East Asian (EAS) AF: 0.473 AC: 18782 AN: 39680

South Asian (SAS) AF: 0.208 AC: 17938 AN: 86186

European-Finnish (FIN) AF: 0.401 AC: 21418 AN: 53394

Middle Eastern (MID) AF: 0.399 AC: 2299 AN: 5762

European-Non Finnish (NFE) AF: 0.388 AC: 430378 AN: 1108998

Other (OTH) AF: 0.360 AC: 21725 AN: 60274

GnomAD4 genome AF: 0.338 AC: 51434 AN: 152032 Hom.: 9707 Cov.: 32 AF XY: 0.340 AC XY: 25288 AN XY: 74308

African (AFR) AF: 0.176 AC: 7296 AN: 41482

American (AMR) AF: 0.460 AC: 7017 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1560 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2192 AN: 5156

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4820

European-Finnish (FIN) AF: 0.392 AC: 4136 AN: 10550

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26915 AN: 67976

Other (OTH) AF: 0.366 AC: 773 AN: 2112

Alfa AF: 0.382 Hom.: 54188

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;.;.
PhyloP100		2.9
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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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