Genetic Variant GBP7:p.Asp393Tyr (chr1-89147755-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207398.3(GBP7):c.1177G>T(p.Asp393Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GBP7
NM_207398.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

Variant links:

Genes affected

GBP7 (HGNC:29606): (guanylate binding protein 7) Guanylate-binding proteins, such as GBP7, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).[supplied by OMIM, Dec 2008]

GBP7 links:

GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

GBP2 links:

LOC105378842 (HGNC:):

LOC105378842 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27403724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP7	NM_207398.3 link	c.1177G>T	p.Asp393Tyr	missense_variant	Exon 8 of 11	ENST00000294671.3	NP_997281.2	Q8N8V2
LOC105378842	XR_001737682.2 link	n.109-832C>A		intron_variant	Intron 1 of 3
LOC105378842	XR_947579.3 link	n.232-836C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GBP7	ENST00000294671.3 link	c.1177G>T	p.Asp393Tyr	missense_variant	Exon 8 of 11	2	NM_207398.3	ENSP00000294671.2	Q8N8V2
GBP7	ENST00000650452.1 link	c.1177G>T	p.Asp393Tyr	missense_variant	Exon 8 of 9			ENSP00000496924.1	A0A3B3IRS3
GBP2	ENST00000464839.5 link	n.-406G>T		non_coding_transcript_exon_variant	Exon 3 of 15	2		ENSP00000434282.1	P32456
GBP2	ENST00000464839.5 link	n.-406G>T		5_prime_UTR_variant	Exon 3 of 15	2		ENSP00000434282.1	P32456

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1177G>T (p.D393Y) alteration is located in exon 8 (coding exon 7) of the GBP7 gene. This alteration results from a G to T substitution at nucleotide position 1177, causing the aspartic acid (D) at amino acid position 393 to be replaced by a tyrosine (Y). 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

0.085

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.017

D;.

Polyphen

0.059

B;.

Vest4

0.17

MutPred

0.63

Loss of disorder (P = 0.0488);Loss of disorder (P = 0.0488);

MVP

0.25

MPC

0.044

ClinPred

0.45

GERP RS

2.1

Varity_R

0.26

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over