rs2289247

Variant names:

• chr3-52693241-G-A
• rs2289247
• NM_014366.5:c.1099G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-52693241-G-A
• chr3-52693241-G-C
• chr3-52693241-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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V367L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.46 (16078 hom., cov: 31)
  • Exomes 𝑓: 0.42 (128470 hom.)
• Consequence: GNL3 NM_014366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 81 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=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 rank	MANE	Protein	UniProt
GNL3	NM_014366.5	c.1099G>A	p.Val367Met	missense_variant	Exon 11 of 15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2	c.1063G>A	p.Val355Met	missense_variant	Exon 11 of 15		NP_996561.1
GNL3	NM_206826.1	c.1063G>A	p.Val355Met	missense_variant	Exon 11 of 15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.1099G>A	p.Val367Met	missense_variant	Exon 11 of 15	1	NM_014366.5	ENSP00000395772.1
GNL3	ENST00000394799.6	c.1063G>A	p.Val355Met	missense_variant	Exon 11 of 15	2		ENSP00000378278.2
GNL3	ENST00000496254.5	n.1383G>A		non_coding_transcript_exon_variant	Exon 10 of 14	5
GNL3	ENST00000497356.1	n.72G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69054 AN: 151684 Hom.: 16058 Cov.: 31

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

GnomAD2 exomes AF: 0.432 AC: 108345 AN: 250910 AF XY: 0.418

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 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.: 35 AF XY: 0.410 AC XY: 298284 AN XY: 726768

African (AFR) AF: 0.533 AC: 17808 AN: 33418

American (AMR) AF: 0.551 AC: 24593 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12482 AN: 26116

East Asian (EAS) AF: 0.478 AC: 18968 AN: 39698

South Asian (SAS) AF: 0.269 AC: 23228 AN: 86190

European-Finnish (FIN) AF: 0.409 AC: 21839 AN: 53400

Middle Eastern (MID) AF: 0.447 AC: 2581 AN: 5768

European-Non Finnish (NFE) AF: 0.415 AC: 461183 AN: 1111250

Other (OTH) AF: 0.410 AC: 24760 AN: 60354

GnomAD4 genome AF: 0.455 AC: 69129 AN: 151802 Hom.: 16078 Cov.: 31 AF XY: 0.454 AC XY: 33705 AN XY: 74178

African (AFR) AF: 0.523 AC: 21612 AN: 41352

American (AMR) AF: 0.521 AC: 7965 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1618 AN: 3464

East Asian (EAS) AF: 0.430 AC: 2217 AN: 5160

South Asian (SAS) AF: 0.270 AC: 1296 AN: 4808

European-Finnish (FIN) AF: 0.399 AC: 4197 AN: 10520

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28698 AN: 67920

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.435 Hom.: 73710

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	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.031	T;T
MetaRNN	Benign	0.000026	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.84	N;.
PhyloP100		0.17
PrimateAI	Benign	0.22	T
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	T
GERP RS		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289247; hg19: chr3-52727257; COSMIC: COSV56476624; COSMIC: COSV56476624;