Variant chr1-89011887-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018284.3(GBP3):c.1009A>G(p.Met337Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000964 in 1,462,332 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000043 ( 2 hom., cov: 26)

Exomes 𝑓: 0.00010 ( 35 hom. )

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBP3	NM_018284.3 linkuse as main transcript	c.1009A>G	p.Met337Val	missense_variant	7/11	ENST00000370481.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBP3	ENST00000370481.9 linkuse as main transcript	c.1009A>G	p.Met337Val	missense_variant	7/11	1	NM_018284.3	P1	Q9H0R5-1

Frequencies

GnomAD3 genomes

AF:

0.0000430

AC:

AN:

139538

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:

0.0000992

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000432

AC:

AN:

231702

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

124854

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000982

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

135

AN:

1322794

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

658592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.0000544

GnomAD4 genome

AF:

0.0000430

AC:

AN:

139538

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

68100

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000992

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000526

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.1009A>G (p.M337V) alteration is located in exon 7 (coding exon 6) of the GBP3 gene. This alteration results from a A to G substitution at nucleotide position 1009, causing the methionine (M) at amino acid position 337 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.84

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

3.9

MutationTaster

Benign

0.99

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.36

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.44

MVP

0.80

MPC

0.19

ClinPred

0.77

GERP RS

2.7

Varity_R

0.57

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over