chr7-2731405-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_007353.3(GNA12):​c.922G>A​(p.Val308Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,670 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 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GNA12
NM_007353.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.35397083).
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNA12NM_007353.3 linkc.922G>A p.Val308Met missense_variant Exon 4 of 4 ENST00000275364.8 NP_031379.2 Q03113-1Q6ZQV4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNA12ENST00000275364.8 linkc.922G>A p.Val308Met missense_variant Exon 4 of 4 1 NM_007353.3 ENSP00000275364.3 Q03113-1

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
151984
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
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
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250818
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135568
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1460686
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
726500
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000921
AC:
14
AN:
151984
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000852
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:
0.0000680
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.922G>A (p.V308M) alteration is located in exon 4 (coding exon 4) of the GNA12 gene. This alteration results from a G to A substitution at nucleotide position 922, causing the valine (V) at amino acid position 308 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
Benign
0.18
BayesDel_addAF
Benign
-0.0063
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;.;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Pathogenic
3.1
M;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Uncertain
0.53
Sift
Uncertain
0.022
D;D;D
Sift4G
Uncertain
0.057
T;D;T
Polyphen
0.96
P;.;.
Vest4
0.42
MVP
0.87
MPC
1.5
ClinPred
0.71
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.69

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.

Other links and lift over

dbSNP: rs368581021; hg19: chr7-2771039; COSMIC: COSV99282919; API