chr1-26897402-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022078.3(GPATCH3):ā€‹c.775A>Gā€‹(p.Ile259Val) 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 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GPATCH3
NM_022078.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
Genes affected
GPATCH3 (HGNC:25720): (G-patch domain containing 3) Predicted to enable nucleic acid binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and positive regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09075189).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPATCH3NM_022078.3 linkuse as main transcriptc.775A>G p.Ile259Val missense_variant 2/7 ENST00000361720.10
GPATCH3XM_047427518.1 linkuse as main transcriptc.775A>G p.Ile259Val missense_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPATCH3ENST00000361720.10 linkuse as main transcriptc.775A>G p.Ile259Val missense_variant 2/71 NM_022078.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727244
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 01, 2023The c.775A>G (p.I259V) alteration is located in exon 2 (coding exon 2) of the GPATCH3 gene. This alteration results from a A to G substitution at nucleotide position 775, causing the isoleucine (I) at amino acid position 259 to be replaced by a valine (V). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.47
N
REVEL
Benign
0.087
Sift
Benign
0.077
T
Sift4G
Benign
0.18
T
Polyphen
0.21
B
Vest4
0.15
MutPred
0.22
Gain of catalytic residue at I259 (P = 0.0905);
MVP
0.19
MPC
0.14
ClinPred
0.59
D
GERP RS
4.7
Varity_R
0.081
gMVP
0.16

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: chr1-27223893; API