chr1-109573759-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_006496.4(GNAI3):​c.141C>A​(p.Ser47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

GNAI3
NM_006496.4 missense

Scores

11
7
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.688
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 Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
Variant 1-109573759-C-A is Pathogenic according to our data. Variant chr1-109573759-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 64691.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-109573759-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNAI3NM_006496.4 linkuse as main transcriptc.141C>A p.Ser47Arg missense_variant 2/9 ENST00000369851.7 NP_006487.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GNAI3ENST00000369851.7 linkuse as main transcriptc.141C>A p.Ser47Arg missense_variant 2/91 NM_006496.4 ENSP00000358867 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Auriculocondylar syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.96
D
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D
M_CAP
Pathogenic
0.64
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Uncertain
0.35
D
MutationAssessor
Pathogenic
4.4
H
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-4.0
D
REVEL
Pathogenic
0.85
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.99
MutPred
0.88
Gain of MoRF binding (P = 0.0056);
MVP
0.93
MPC
1.7
ClinPred
1.0
D
GERP RS
2.9
Varity_R
0.97
gMVP
0.96

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: rs397514768; hg19: chr1-110116381; API