chr1-89369606-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198460.3(GBP6):​c.251C>T​(p.Pro84Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GBP6
NM_198460.3 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96
Variant links:
Genes affected
GBP6 (HGNC:25395): (guanylate binding protein family member 6) Guanylate-binding proteins, such as GBP6, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).[supplied by OMIM, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBP6NM_198460.3 linkc.251C>T p.Pro84Leu missense_variant Exon 3 of 11 ENST00000370456.5 NP_940862.2 Q6ZN66-1
GBP6XM_011540835.4 linkc.251C>T p.Pro84Leu missense_variant Exon 3 of 11 XP_011539137.1 Q6ZN66-1
GBP6NM_001320257.2 linkc.-73+5479C>T intron_variant Intron 1 of 8 NP_001307186.1 B4E1U2B4DRX0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBP6ENST00000370456.5 linkc.251C>T p.Pro84Leu missense_variant Exon 3 of 11 1 NM_198460.3 ENSP00000359485.5 Q6ZN66-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251270
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135782
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461712
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727144
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.251C>T (p.P84L) alteration is located in exon 3 (coding exon 2) of the GBP6 gene. This alteration results from a C to T substitution at nucleotide position 251, causing the proline (P) at amino acid position 84 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
0.20
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.98
D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Pathogenic
4.3
H
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-8.5
D
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.84
Loss of glycosylation at P84 (P = 0.0461);
MVP
0.84
MPC
0.37
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.86
gMVP
0.93

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.

Other links and lift over

dbSNP: rs773035311; hg19: chr1-89835165; API