NM_014366.5:c.931G>T

Variant names:

• chr3-52692933-G-T
• rs746795082
• NM_014366.5:c.931G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014366.5(GNL3):​c.931G>T​(p.Val311Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GNL3 NM_014366.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08

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]

SNORD69 (HGNC:32730): (small nucleolar RNA, C/D box 69)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2109952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNL3	NM_014366.5	c.931G>T	p.Val311Leu	missense_variant	Exon 10 of 15	ENST00000418458.6	NP_055181.3
GNL3	NM_206825.2	c.895G>T	p.Val299Leu	missense_variant	Exon 10 of 15		NP_996561.1
GNL3	NM_206826.1	c.895G>T	p.Val299Leu	missense_variant	Exon 10 of 15		NP_996562.1
SNORD69	NR_003057.1	n.*121G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.931G>T	p.Val311Leu	missense_variant	Exon 10 of 15	1	NM_014366.5	ENSP00000395772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461068 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726920

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.80	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.073
Sift	Benign	0.28	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.012	B;.
Vest4		0.34
MutPred		0.45		Loss of catalytic residue at V311 (P = 0.1146);.;
MVP		0.29
MPC		0.27
ClinPred		0.92	D
GERP RS		5.0
Varity_R		0.064
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs746795082; hg19: chr3-52726949;