Variant 7-80135244-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.84G>C(p.Glu28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GNAI1
NM_002069.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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:

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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=0.38622677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI1	NM_002069.6 link	c.84G>C	p.Glu28Asp	missense_variant	1/8	ENST00000649796.2	NP_002060.4	P63096-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649796.2 link	c.84G>C	p.Glu28Asp	missense_variant	1/8		NM_002069.6	ENSP00000497260.1		P63096-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1384574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.31e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.84G>C (p.E28D) alteration is located in exon 1 (coding exon 1) of the GNAI1 gene. This alteration results from a G to C substitution at nucleotide position 84, causing the glutamic acid (E) at amino acid position 28 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.0054

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

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

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.89

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

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.39

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

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.1

L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.0

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

REVEL

Uncertain

0.31

Sift

Benign

0.28

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

Sift4G

Benign

0.40

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

Polyphen

0.0

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

Vest4

0.15

MutPred

0.35

Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);

MVP

0.69

MPC

0.84

ClinPred

0.71

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over