Variant chr7-2731321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007353.3(GNA12):c.1006G>A(p.Asp336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GNA12
NM_007353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

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: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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15034541).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	4/4	ENST00000275364.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	4/4	1	NM_007353.3	P1	Q03113-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251330

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 11, 2023

The c.1006G>A (p.D336N) 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 1006, causing the aspartic acid (D) at amino acid position 336 to be replaced by an asparagine (N). 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

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.020

N;.;.

MutationTaster

Benign

0.91

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.29

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.013

B;.;.

Vest4

0.11

MutPred

0.44

Gain of MoRF binding (P = 0.0623);.;.;

MVP

0.67

MPC

0.63

ClinPred

0.18

GERP RS

4.1

Varity_R

0.092

gMVP

0.32

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