1-37568987-C-T

Variant names:

• chr1-37568987-C-T
• NM_013285.3:c.1732G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013285.3(GNL2):​c.1732G>A​(p.Glu578Lys) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNL2 NM_013285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

GNL2 (HGNC:29925): (G protein nucleolar 2) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11499694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL2	NM_013285.3	MANE Select	c.1732G>A	p.Glu578Lys	missense	Exon 13 of 16	NP_037417.1	Q5T0F3
	GNL2	NM_001323623.2		c.1936G>A	p.Glu646Lys	missense	Exon 14 of 17	NP_001310552.1
	GNL2	NM_001323624.2		c.1183G>A	p.Glu395Lys	missense	Exon 12 of 15	NP_001310553.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL2	ENST00000373062.8	TSL:1 MANE Select	c.1732G>A	p.Glu578Lys	missense	Exon 13 of 16	ENSP00000362153.3	Q13823
	GNL2	ENST00000852774.1		c.1759G>A	p.Glu587Lys	missense	Exon 13 of 16	ENSP00000522833.1
	GNL2	ENST00000965152.1		c.1729G>A	p.Glu577Lys	missense	Exon 13 of 16	ENSP00000635211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.11
Sift	Benign	0.26	T
Sift4G	Benign	0.54	T
Polyphen		0.27	B
Vest4		0.090
MutPred		0.19		Gain of ubiquitination at E578 (P = 0.0066)
MVP		0.30
MPC		0.14
ClinPred		0.21	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.19
Mutation Taster		=92/8	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

hg19: chr1-38034588;