Variant 7-80188965-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001256414.2(GNAI1):c.-24G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNAI1
NM_001256414.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.988

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI1	NM_002069.6 link	c.133G>T	p.Gly45Cys	missense_variant	2/8	ENST00000649796.2	NP_002060.4	P63096-1
GNAI1	NM_001256414.2 link	c.-24G>T		5_prime_UTR_premature_start_codon_gain_variant	2/8		NP_001243343.1	P63096-2
GNAI1	NM_001256414.2 link	c.-24G>T		5_prime_UTR_variant	2/8		NP_001243343.1	P63096-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649796.2 link	c.133G>T	p.Gly45Cys	missense_variant	2/8		NM_002069.6	ENSP00000497260.1		P63096-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724042

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:

0.00

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

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Mar 30, 2023

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.58

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

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

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

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

M_CAP

Pathogenic

0.49

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.7

H;H;H;H;H;H;H;H;H;H;H;H;H;H;H;.

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-7.1

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

REVEL

Pathogenic

0.97

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.85

MutPred

0.94

Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);

MVP

0.99

MPC

2.1

ClinPred

1.0

GERP RS

5.9

Varity_R

0.97

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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