Variant 7-2762657-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282440.1(GNA12):c.232A>G(p.Ile78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,598,710 control chromosomes in the GnomAD database, including 203 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 74 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 129 hom. )

Consequence

GNA12
NM_001282440.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Variant links:

Genes affected

GNA12 (HGNC:4380): (G protein subunit alpha 12) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Involved in regulation of TOR signaling and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

GNA12 links:

AMZ1 (HGNC:):

AMZ1 links:

AMZ1 (HGNC:22231): (archaelysin family metallopeptidase 1) Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

AMZ1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002007693).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA12	NM_007353.3 linkuse as main transcript	c.526-29156A>G		intron_variant		ENST00000275364.8	NP_031379.2	Q03113-1Q6ZQV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8 linkuse as main transcript	c.526-29156A>G		intron_variant		1	NM_007353.3	ENSP00000275364.3		Q03113-1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3232

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.00756

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0105

AC:

2349

AN:

223436

Hom.:

AF XY:

0.0102

AC XY:

1249

AN XY:

122358

show subpopulations

Gnomad AFR exome

AF:

0.0588

Gnomad AMR exome

AF:

0.00891

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.000180

Gnomad SAS exome

AF:

0.00515

Gnomad FIN exome

AF:

0.000768

Gnomad NFE exome

AF:

0.00903

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00892

AC:

12908

AN:

1446480

Hom.:

129

Cov.:

AF XY:

0.00874

AC XY:

6276

AN XY:

718240

show subpopulations

Gnomad4 AFR exome

AF:

0.0571

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.00495

Gnomad4 FIN exome

AF:

0.00102

Gnomad4 NFE exome

AF:

0.00783

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0213

AC:

3239

AN:

152230

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

1559

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0556

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.00636

Hom.:

Bravo

AF:

0.0254

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0514

AC:

ESP6500EA

AF:

0.00879

AC:

ExAC

AF:

0.0107

AC:

1255

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.20

DANN

Benign

0.63

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.83

PROVEAN

Benign

-0.11

REVEL

Benign

0.070

Sift

Uncertain

0.012

Sift4G

Benign

0.34

Vest4

0.021

ClinPred

0.0029

GERP RS

-3.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over