Variant 7-2843990-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007353.3(GNA12):c.172G>A(p.Val58Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000841 in 1,427,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

GNA12
NM_007353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3 linkuse as main transcript	c.172G>A	p.Val58Met	missense_variant	1/4	ENST00000275364.8
GNA12	NM_001293092.2 linkuse as main transcript	c.172G>A	p.Val58Met	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8 linkuse as main transcript	c.172G>A	p.Val58Met	missense_variant	1/4	1	NM_007353.3	P1	Q03113-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000194

AC:

AN:

206632

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

113488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000212

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000841

AC:

AN:

1427190

Hom.:

Cov.:

AF XY:

0.00000846

AC XY:

AN XY:

709188

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:

0.000117

Gnomad4 NFE exome

AF:

0.00000456

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.172G>A (p.V58M) alteration is located in exon 1 (coding exon 1) of the GNA12 gene. This alteration results from a G to A substitution at nucleotide position 172, causing the valine (V) at amino acid position 58 to be replaced by a methionine (M). 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

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.67

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.58

Sift

Benign

0.031

Sift4G

Uncertain

0.0020

Polyphen

0.93

Vest4

0.40

MutPred

0.61

Loss of methylation at K59 (P = 0.0227);

MVP

0.88

MPC

1.6

ClinPred

0.62

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.72

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