Variant chr7-80135197-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002069.6(GNAI1):c.37G>C(p.Val13Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,556,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

GNAI1
NM_002069.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

GNAI1 (HGNC:4384): (G protein subunit alpha i1) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The alpha subunit binds guanine nucleotide, can hydrolyze GTP, and can interact with other proteins. The protein encoded by this gene represents the alpha subunit of an inhibitory complex. The encoded protein is part of a complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GNAI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29067746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI1	NM_002069.6 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	1/8	ENST00000649796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI1	ENST00000649796.2 linkuse as main transcript	c.37G>C	p.Val13Leu	missense_variant	1/8		NM_002069.6	P1	P63096-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1403912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697932

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2022

Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.28

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.089

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.86

.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;D

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.70

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.5

.;.;.;.;.;.;.;.;.;.;N;.;.;N;.;.

REVEL

Benign

0.25

Sift

Benign

0.65

.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.

Sift4G

Benign

0.31

.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.

Polyphen

0.0

B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;.

Vest4

0.096

MutPred

0.38

Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);Loss of MoRF binding (P = 0.0978);

MVP

0.42

MPC

0.90

ClinPred

0.94

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.56

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