chr1-109548782-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006496.4(GNAI3):​c.62G>A​(p.Arg21His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,612,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

GNAI3
NM_006496.4 missense

Scores

2
12
5

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.025603741).
BP6
Variant 1-109548782-G-A is Benign according to our data. Variant chr1-109548782-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034301.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNAI3NM_006496.4 linkuse as main transcriptc.62G>A p.Arg21His 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.62G>A p.Arg21His missense_variant 1/91 NM_006496.4 ENSP00000358867 P1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000391
AC:
97
AN:
248140
Hom.:
1
AF XY:
0.000246
AC XY:
33
AN XY:
134370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00234
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:
0.00
Gnomad OTH exome
AF:
0.00281
GnomAD4 exome
AF:
0.0000739
AC:
108
AN:
1460796
Hom.:
0
Cov.:
30
AF XY:
0.0000537
AC XY:
39
AN XY:
726592
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00229
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:
0.0000994
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000916
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000422
Hom.:
0
Bravo
AF:
0.000193
ExAC
AF:
0.000577
AC:
70

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

GNAI3-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 09, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.87
D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.026
T
MetaSVM
Uncertain
0.32
D
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.3
N
REVEL
Uncertain
0.55
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.052
T
Polyphen
0.83
P
Vest4
0.41
MutPred
0.50
Loss of MoRF binding (P = 0.0083);
MVP
0.96
MPC
1.2
ClinPred
0.14
T
GERP RS
5.9
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.71
gMVP
0.30

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: rs758232853; hg19: chr1-110091404; API