dbSNP rs7371: GNAI3:c.*364G>A (chr1-109592686-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006496.4(GNAI3):c.*364G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,872 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2542 hom., cov: 32)

Exomes 𝑓: 0.20 ( 19 hom. )

Consequence

GNAI3
NM_006496.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

18 publications found

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]

GNAI3 Gene-Disease associations (from GenCC):

auriculocondylar syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
auriculocondylar syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GNAI3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAI3	NM_006496.4 link	c.*364G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000369851.7	NP_006487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAI3	ENST00000369851.7 link	c.*364G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_006496.4	ENSP00000358867.4

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26669

AN:

151822

Hom.:

2545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.200

AC:

186

AN:

930

Hom.:

Cov.:

AF XY:

0.225

AC XY:

113

AN XY:

502

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.220

AC:

AN:

440

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.173

AC:

AN:

382

Other (OTH)

AF:

0.192

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26683

AN:

151942

Hom.:

2542

Cov.:

AF XY:

0.179

AC XY:

13288

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.134

AC:

5531

AN:

41414

American (AMR)

AF:

0.165

AC:

2512

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

795

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1749

AN:

5178

South Asian (SAS)

AF:

0.304

AC:

1460

AN:

4806

European-Finnish (FIN)

AF:

0.195

AC:

2058

AN:

10562

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11924

AN:

67936

Other (OTH)

AF:

0.185

AC:

391

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1099

2198

3297

4396

5495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.167

Hom.:

2726

Bravo

AF:

0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

(source)

DANN

Benign

0.51

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over