Variant chr1-109548825-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006496.4(GNAI3):c.105G>A(p.Lys35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 1,532,620 control chromosomes in the GnomAD database, including 856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 59 hom., cov: 32)

Exomes 𝑓: 0.032 ( 797 hom. )

Consequence

GNAI3
NM_006496.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 1-109548825-G-A is Benign according to our data. Variant chr1-109548825-G-A is described in ClinVar as [Benign]. Clinvar id is 1243082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0234 (3563/152322) while in subpopulation NFE AF= 0.033 (2245/68012). AF 95% confidence interval is 0.0319. There are 59 homozygotes in gnomad4. There are 1767 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3563 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI3	NM_006496.4 linkuse as main transcript	c.105G>A	p.Lys35=	synonymous_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.105G>A	p.Lys35=	synonymous_variant	1/9	1	NM_006496.4	ENSP00000358867	P1

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3564

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00535

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0251

AC:

6094

AN:

242420

Hom.:

127

AF XY:

0.0249

AC XY:

3260

AN XY:

131022

show subpopulations

Gnomad AFR exome

AF:

0.00556

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00740

Gnomad FIN exome

AF:

0.0574

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0318

AC:

43846

AN:

1380298

Hom.:

797

Cov.:

AF XY:

0.0310

AC XY:

21349

AN XY:

689654

show subpopulations

Gnomad4 AFR exome

AF:

0.00589

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.00724

Gnomad4 FIN exome

AF:

0.0554

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0234

AC:

3563

AN:

152322

Hom.:

Cov.:

AF XY:

0.0237

AC XY:

1767

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00534

Gnomad4 AMR

AF:

0.0207

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.0527

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0203

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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