Genetic Variant GNL3:p.Val367Leu (chr3-52693241-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014366.5(GNL3):c.1099G>T(p.Val367Leu) 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. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNL3
NM_014366.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.172

Publications

0 publications found

Variant links:

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]

GNL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNL3	NM_014366.5	MANE Select	c.1099G>T	p.Val367Leu	missense	Exon 11 of 15	NP_055181.3
GNL3	NM_206825.2		c.1063G>T	p.Val355Leu	missense	Exon 11 of 15	NP_996561.1	Q9BVP2-2
GNL3	NM_206826.1		c.1063G>T	p.Val355Leu	missense	Exon 11 of 15	NP_996562.1	Q9BVP2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNL3	ENST00000418458.6	TSL:1 MANE Select	c.1099G>T	p.Val367Leu	missense	Exon 11 of 15	ENSP00000395772.1	Q9BVP2-1
GNL3	ENST00000858565.1		c.1096G>T	p.Val366Leu	missense	Exon 11 of 15	ENSP00000528624.1
GNL3	ENST00000931677.1		c.1096G>T	p.Val366Leu	missense	Exon 11 of 15	ENSP00000601736.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727096

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111814

Other (OTH)

AF:

0.00

AC:

AN:

60382

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.1

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.045

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.043

M_CAP

Benign

0.0047

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.4

PhyloP100

0.17

PrimateAI

Benign

0.23

PROVEAN

Benign

1.8

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.077

MutPred

0.43

Gain of sheet (P = 1e-04)

MVP

0.20

MPC

0.098

ClinPred

0.041

GERP RS

0.48

Varity_R

0.044

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over