Variant 1-109548649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006496.4(GNAI3):c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,040,390 control chromosomes in the GnomAD database, including 22,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2788 hom., cov: 32)

Exomes 𝑓: 0.20 ( 19407 hom. )

Consequence

GNAI3
NM_006496.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0100

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-109548649-C-T is Benign according to our data. Variant chr1-109548649-C-T is described in ClinVar as [Benign]. Clinvar id is 1274531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI3	NM_006496.4 linkuse as main transcript	c.-72C>T		5_prime_UTR_variant	1/9	ENST00000369851.7	NP_006487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI3	ENST00000369851.7 linkuse as main transcript	c.-72C>T		5_prime_UTR_variant	1/9	1	NM_006496.4	ENSP00000358867	P1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27809

AN:

152028

Hom.:

2789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.201

AC:

178615

AN:

888242

Hom.:

19407

Cov.:

AF XY:

0.205

AC XY:

93668

AN XY:

457828

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.183

AC:

27824

AN:

152148

Hom.:

2788

Cov.:

AF XY:

0.186

AC XY:

13810

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.182

Hom.:

420

Bravo

AF:

0.176

Asia WGS

AF:

0.296

AC:

1027

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.1

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over