Variant chr1-89011928-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018284.3(GBP3):c.968C>T(p.Ser323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,462,320 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 1 hom., cov: 26)

Exomes 𝑓: 0.000015 ( 6 hom. )

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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:

GBP3 (HGNC:):

GBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2626).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP3	NM_018284.3 linkuse as main transcript	c.968C>T	p.Ser323Leu	missense_variant	7/11	ENST00000370481.9	NP_060754.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBP3	ENST00000370481.9 linkuse as main transcript	c.968C>T	p.Ser323Leu	missense_variant	7/11	1	NM_018284.3	ENSP00000359512.4		Q9H0R5-1

Frequencies

GnomAD3 genomes

AF:

0.0000215

AC:

AN:

139576

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:

0.0000496

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000302

AC:

AN:

231612

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

124812

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:

0.0000688

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1322744

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

658558

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:

0.0000181

Gnomad4 OTH exome

AF:

0.0000363

GnomAD4 genome

AF:

0.0000215

AC:

AN:

139576

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

68088

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:

0.0000496

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000879

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

Nov 22, 2023

The c.968C>T (p.S323L) alteration is located in exon 7 (coding exon 6) of the GBP3 gene. This alteration results from a C to T substitution at nucleotide position 968, causing the serine (S) at amino acid position 323 to be replaced by a leucine (L). 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

0.089

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.80

M_CAP

Benign

0.0031

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.14

Sift

Benign

0.054

Sift4G

Uncertain

0.038

Polyphen

0.17

Vest4

0.33

MutPred

0.53

Loss of disorder (P = 0.0736);

MVP

0.37

MPC

0.047

ClinPred

0.29

GERP RS

3.8

Varity_R

0.29

gMVP

0.25

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

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