Genetic Variant GPN3:p.Glu276Lys (chr12-110453063-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016301.4(GPN3):c.826G>A(p.Glu276Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,478,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

GPN3
NM_016301.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Publications

0 publications found

Variant links:

Genes affected

GPN3 (HGNC:30186): (GPN-loop GTPase 3) Predicted to enable GTPase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

GPN3 links:

ENSG00000300534 (HGNC:):

ENSG00000300534 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.07923216).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPN3	NM_016301.4	MANE Select	c.826G>A	p.Glu276Lys	missense	Exon 8 of 8	NP_057385.3
GPN3	NM_001164372.2		c.943G>A	p.Glu315Lys	missense	Exon 8 of 8	NP_001157844.1	Q9UHW5-3
GPN3	NM_001164373.2		c.856G>A	p.Glu286Lys	missense	Exon 8 of 8	NP_001157845.1	Q9UHW5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPN3	ENST00000228827.8	TSL:1 MANE Select	c.826G>A	p.Glu276Lys	missense	Exon 8 of 8	ENSP00000228827.3	Q9UHW5-1
GPN3	ENST00000537466.6	TSL:1	c.856G>A	p.Glu286Lys	missense	Exon 8 of 8	ENSP00000443068.2	Q9UHW5-2
GPN3	ENST00000543199.5	TSL:5	c.943G>A	p.Glu315Lys	missense	Exon 8 of 8	ENSP00000442770.1	Q9UHW5-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

246942

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000905

AC:

AN:

1326302

Hom.:

Cov.:

AF XY:

0.00000900

AC XY:

AN XY:

666778

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

30894

American (AMR)

AF:

0.00

AC:

AN:

44108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25262

East Asian (EAS)

AF:

0.0000512

AC:

AN:

39074

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.00000202

AC:

AN:

989560

Other (OTH)

AF:

0.0000179

AC:

AN:

55920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.054

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.018

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

4.9

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.24

REVEL

Benign

0.12

Sift

Benign

0.079

Sift4G

Benign

0.13

Polyphen

0.041

Vest4

0.42

MVP

0.33

MPC

0.40

ClinPred

0.12

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.60

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over