chr3-52687289-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014366.5(GNL3):​c.116G>C​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: not found (cov: 32)
• Consequence: GNL3 NM_014366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32487565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014366.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL3	NM_014366.5	MANE Select	c.116G>C	p.Arg39Pro	missense	Exon 3 of 15	NP_055181.3
	GNL3	NM_206825.2		c.80G>C	p.Arg27Pro	missense	Exon 3 of 15	NP_996561.1
	GNL3	NM_206826.1		c.80G>C	p.Arg27Pro	missense	Exon 3 of 15	NP_996562.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL3	ENST00000418458.6	TSL:1 MANE Select	c.116G>C	p.Arg39Pro	missense	Exon 3 of 15	ENSP00000395772.1
	GNL3	ENST00000394799.6	TSL:2	c.80G>C	p.Arg27Pro	missense	Exon 3 of 15	ENSP00000378278.2
	GNL3	ENST00000479230.5	TSL:4	c.80G>C	p.Arg27Pro	missense	Exon 3 of 6	ENSP00000419734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.083
Sift	Benign	0.072	T
Sift4G	Benign	0.17	T
Polyphen		0.030	B
Vest4		0.42
MutPred		0.31		Gain of loop (P = 0.0166)
MVP		0.65
MPC		0.58
ClinPred		0.97	D
GERP RS		1.9
Varity_R		0.82
gMVP		0.16
Mutation Taster		=64/36	polymorphism

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;