Genetic Variant GBP3:p.Ala325Ser (chr1-89011923-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018284.3(GBP3):c.973G>T(p.Ala325Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A325T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

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>T	p.Ala325Ser	missense	Exon 7 of 11	NP_060754.2	Q9H0R5-1
GBP3	NM_001436844.1		c.973G>T	p.Ala325Ser	missense	Exon 7 of 11	NP_001423773.1	A0ABB0MVI2
GBP3	NM_001319181.2		c.973G>T	p.Ala325Ser	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>T	p.Ala325Ser	missense	Exon 7 of 11	ENSP00000359512.4	Q9H0R5-1
GBP3	ENST00000493594.6	TSL:1	n.*783G>T		non_coding_transcript_exon	Exon 8 of 12	ENSP00000456449.1	H3BRX6
GBP3	ENST00000493594.6	TSL:1	n.*783G>T		3_prime_UTR	Exon 8 of 12	ENSP00000456449.1	H3BRX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000863

AC:

AN:

231622

AF XY:

0.00

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:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000151

AC:

AN:

1322732

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

658558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.00

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:

0.00

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:

0.00000201

AC:

AN:

994822

Other (OTH)

AF:

0.00

AC:

AN:

55108

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0042

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

4.2

PhyloP100

4.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.49

MutPred

0.88

Gain of disorder (P = 0.0363)

MVP

0.44

MPC

0.28

ClinPred

0.99

GERP RS

3.8

PromoterAI

0.015

Neutral

(source)

Varity_R

0.76

gMVP

0.22

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over