chr1-89009454-G-A

Position:

• chr1-89009454-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018284.3(GBP3):​c.1403C>T​(p.Ser468Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GBP3 NM_018284.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25376973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP3	NM_018284.3	c.1403C>T	p.Ser468Phe	missense_variant	9/11	ENST00000370481.9	NP_060754.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBP3	ENST00000370481.9	c.1403C>T	p.Ser468Phe	missense_variant	9/11	1	NM_018284.3	ENSP00000359512.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.1403C>T (p.S468F) alteration is located in exon 9 (coding exon 8) of the GBP3 gene. This alteration results from a C to T substitution at nucleotide position 1403, causing the serine (S) at amino acid position 468 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.061
Sift	Benign	0.12	T;T
Sift4G	Benign	0.58	T;D
Polyphen		0.32	B;.
Vest4		0.34
MutPred		0.30		Loss of disorder (P = 0.0088);.;
MVP		0.30
MPC		0.054
ClinPred		0.21	T
GERP RS		-1.3
Varity_R		0.17
gMVP		0.082

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-89475137;