NM_002053.3:c.1339T>C

Variant names:

• chr1-89056045-A-G
• NM_002053.3:c.1339T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002053.3(GBP1):​c.1339T>C​(p.Tyr447His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBP1 NM_002053.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

Genes affected

GBP1 (HGNC:4182): (guanylate binding protein 1) Guanylate binding protein expression is induced by interferon. Guanylate binding proteins are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP) and are distinguished from the GTP-binding proteins by the presence of 2 binding motifs rather than 3. [provided by RefSeq, Jul 2008]

LOC105378841 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3	c.1339T>C	p.Tyr447His	missense_variant	Exon 8 of 11	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3207+9125A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.1339T>C	p.Tyr447His	missense_variant	Exon 8 of 11	1	NM_002053.3	ENSP00000359504.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1339T>C (p.Y447H) alteration is located in exon 8 (coding exon 7) of the GBP1 gene. This alteration results from a T to C substitution at nucleotide position 1339, causing the tyrosine (Y) at amino acid position 447 to be replaced by a histidine (H). 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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	4.2	H
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.85		Gain of methylation at K446 (P = 0.0508);
MVP		0.45
MPC		0.47
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.95
gMVP		0.60

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: chr1-89521728;