NM_014366.5:c.53G>T

Variant names:

• chr3-52686808-G-T
• NM_014366.5:c.53G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014366.5(GNL3):​c.53G>T​(p.Arg18Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GNL3 NM_014366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.62

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNL3	NM_014366.5	c.53G>T	p.Arg18Leu	missense_variant	Exon 2 of 15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2	c.17G>T	p.Arg6Leu	missense_variant	Exon 2 of 15		NP_996561.1
GNL3	NM_206826.1	c.17G>T	p.Arg6Leu	missense_variant	Exon 2 of 15		NP_996562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.53G>T	p.Arg18Leu	missense_variant	Exon 2 of 15	1	NM_014366.5	ENSP00000395772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460008 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726466

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;D;.;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.85	D;D;D;D
MetaSVM	Uncertain	0.093	D
MutationAssessor	Pathogenic	3.3	.;M;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.83, 0.74
MutPred		0.71		.;Loss of methylation at K17 (P = 0.0613);.;.;
MVP		0.90
MPC		0.57
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.90
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52720824;