Genetic Variant GBP3:p.Gly423Glu (chr1-89010998-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_018284.3(GBP3):c.1268G>A(p.Gly423Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,461,572 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000019 ( 7 hom. )

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Publications

1 publications found

Variant links:

Genes affected

GBP3 (HGNC:4184): (guanylate binding protein 3) This gene encodes a member of the guanylate-binding protein (GBP) family. GBPs specifically bind guanine nucleotides (GMP, GDP, and GTP) and contain two of the three consensus motifs found in typical GTP-binding proteins. The encoded protein interacts with a member of the germinal center kinase family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2017]

GBP3 links:

ENSG00000307222 (HGNC:):

ENSG00000307222 links:

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ACMG classification

Classification was made for transcript

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

PP3

MetaRNN computational evidence supports a deleterious effect, 0.981

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018284.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBP3	NM_018284.3	MANE Select	c.1268G>A	p.Gly423Glu	missense	Exon 8 of 11	NP_060754.2	Q9H0R5-1
GBP3	NM_001436844.1		c.1187G>A	p.Gly396Glu	missense	Exon 8 of 11	NP_001423773.1	A0ABB0MVI2
GBP3	NM_001319181.2		c.1187G>A	p.Gly396Glu	missense	Exon 8 of 10	NP_001306110.1	Q9H0R5-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBP3	ENST00000370481.9	TSL:1 MANE Select	c.1268G>A	p.Gly423Glu	missense	Exon 8 of 11	ENSP00000359512.4	Q9H0R5-1
GBP3	ENST00000493594.6	TSL:1	n.*1078G>A		non_coding_transcript_exon	Exon 9 of 12	ENSP00000456449.1	H3BRX6
GBP3	ENST00000493594.6	TSL:1	n.*1078G>A		3_prime_UTR	Exon 9 of 12	ENSP00000456449.1	H3BRX6

Frequencies

GnomAD3 genomes

AF:

0.00000721

AC:

AN:

138776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000166

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

231848

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1322796

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

658636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33242

American (AMR)

AF:

0.00

AC:

AN:

42462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22710

East Asian (EAS)

AF:

0.00

AC:

AN:

38374

South Asian (SAS)

AF:

0.00

AC:

AN:

80454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5308

European-Non Finnish (NFE)

AF:

0.0000231

AC:

AN:

994854

Other (OTH)

AF:

0.0000363

AC:

AN:

55102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00000721

AC:

AN:

138776

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40510

American (AMR)

AF:

0.00

AC:

AN:

13428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2998

East Asian (EAS)

AF:

0.00

AC:

AN:

4840

South Asian (SAS)

AF:

0.00

AC:

AN:

4230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

60294

Other (OTH)

AF:

0.00

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000864

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

0.33

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.41

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0056

MetaRNN

Pathogenic

0.98

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.8

PhyloP100

5.5

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.24

Sift

Uncertain

0.028

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.70

MutPred

0.89

Loss of catalytic residue at A422 (P = 0.0319)

MVP

0.44

MPC

0.28

ClinPred

0.97

GERP RS

3.8

Varity_R

0.69

gMVP

0.25

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over