Variant 1-109548660-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.-61C>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 0.0997 in 1,217,582 control chromosomes in the GnomAD database, including 6,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 930 hom., cov: 32)

Exomes 𝑓: 0.099 ( 5728 hom. )

Consequence

GNAI3
NM_006496.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.535

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-109548660-C-T is Benign according to our data. Variant chr1-109548660-C-T is described in ClinVar as [Benign]. Clinvar id is 1262343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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.-61C>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.-61C>T		5_prime_UTR_variant	1/9	1	NM_006496.4	ENSP00000358867	P1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16078

AN:

152056

Hom.:

932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.0819

Gnomad ASJ

AF:

0.0626

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0482

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.0987

GnomAD4 exome

AF:

0.0989

AC:

105348

AN:

1065410

Hom.:

5728

Cov.:

AF XY:

0.0994

AC XY:

53842

AN XY:

541504

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0623

Gnomad4 ASJ exome

AF:

0.0627

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0512

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.106

AC:

16081

AN:

152172

Hom.:

930

Cov.:

AF XY:

0.102

AC XY:

7624

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0816

Gnomad4 ASJ

AF:

0.0626

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0482

Gnomad4 NFE

AF:

0.0991

Gnomad4 OTH

AF:

0.0976

Alfa

AF:

0.0597

Hom.:

Bravo

AF:

0.110

Asia WGS

AF:

0.0960

AC:

334

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.2

DANN

Benign

0.78

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