Genetic Variant NM_018284.3:c.973G>A (chr1-89011923-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018284.3(GBP3):c.973G>A(p.Ala325Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,462,278 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 5 hom., cov: 26)

Exomes 𝑓: 0.000036 ( 10 hom. )

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 5 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.973G>A	p.Ala325Thr	missense	Exon 7 of 11	NP_060754.2	Q9H0R5-1
GBP3	NM_001436844.1		c.973G>A	p.Ala325Thr	missense	Exon 7 of 11	NP_001423773.1	A0ABB0MVI2
GBP3	NM_001319181.2		c.973G>A	p.Ala325Thr	missense	Exon 7 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.973G>A	p.Ala325Thr	missense	Exon 7 of 11	ENSP00000359512.4	Q9H0R5-1
GBP3	ENST00000493594.6	TSL:1	n.*783G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000456449.1	H3BRX6
GBP3	ENST00000493594.6	TSL:1	n.*783G>A		3_prime_UTR	Exon 8 of 12	ENSP00000456449.1	H3BRX6

Frequencies

GnomAD3 genomes

AF:

0.0000430

AC:

AN:

139434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000739

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000220

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:

0.00

GnomAD2 exomes

AF:

0.0000432

AC:

AN:

231622

AF XY:

0.0000401

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000912

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000982

Gnomad OTH exome

AF:

0.000362

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1322732

Hom.:

Cov.:

AF XY:

0.0000380

AC XY:

AN XY:

658558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.000141

AC:

AN:

42438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22712

East Asian (EAS)

AF:

0.00

AC:

AN:

38370

South Asian (SAS)

AF:

0.000137

AC:

AN:

80464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5292

European-Non Finnish (NFE)

AF:

0.00000905

AC:

AN:

994822

Other (OTH)

AF:

0.000399

AC:

AN:

55108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.000143

AC:

AN:

139546

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

68120

show subpopulations

African (AFR)

AF:

0.0000737

AC:

AN:

40722

American (AMR)

AF:

0.000220

AC:

AN:

13644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3000

East Asian (EAS)

AF:

0.00

AC:

AN:

4854

South Asian (SAS)

AF:

0.00

AC:

AN:

4286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60438

Other (OTH)

AF:

0.00758

AC:

AN:

1846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.0000843

Hom.:

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000615

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

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0043

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.9

PhyloP100

4.2

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.45

MVP

0.45

MPC

0.21

ClinPred

0.82

GERP RS

3.8

PromoterAI

0.015

Neutral

(source)

Varity_R

0.56

gMVP

0.30

Mutation Taster

=93/7

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over