chr1-109548799-G-A

Variant summary

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

The NM_006496.4(GNAI3):​c.79G>A​(p.Gly27Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GNAI3
NM_006496.4 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28
Variant links:
Genes affected
GNAI3 (HGNC:4387): (G protein subunit alpha i3) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

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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=0.3867489).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNAI3NM_006496.4 linkuse as main transcriptc.79G>A p.Gly27Arg missense_variant 1/9 ENST00000369851.7 NP_006487.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GNAI3ENST00000369851.7 linkuse as main transcriptc.79G>A p.Gly27Arg missense_variant 1/91 NM_006496.4 ENSP00000358867 P1

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
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 19, 2024The c.79G>A (p.G27R) alteration is located in exon 1 (coding exon 1) of the GNAI3 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the glycine (G) at amino acid position 27 to be replaced by an arginine (R). 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
0.34
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.39
T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Benign
0.68
N
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.9
D
REVEL
Uncertain
0.39
Sift
Benign
0.036
D
Sift4G
Benign
0.51
T
Polyphen
0.39
B
Vest4
0.25
MutPred
0.38
Gain of methylation at K32 (P = 0.0436);
MVP
0.94
MPC
0.85
ClinPred
0.90
D
GERP RS
5.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.86
gMVP
0.52

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: chr1-110091421; API