Genetic Variant GNA12:c.*2254G>A (chr7-2728927-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007353.3(GNA12):c.*2254G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,306 control chromosomes in the GnomAD database, including 17,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17224 hom., cov: 33)

Exomes 𝑓: 0.38 ( 10 hom. )

Consequence

GNA12
NM_007353.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA12	NM_007353.3 link	c.*2254G>A		3_prime_UTR_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
GNA12	ENST00000275364.8 link	c.*2254G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_007353.3	ENSP00000275364.3		Q03113-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70663

AN:

152044

Hom.:

17192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.382

AC:

AN:

144

Hom.:

Cov.:

AF XY:

0.378

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.387

AC:

AN:

124

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.465

AC:

70744

AN:

152162

Hom.:

17224

Cov.:

AF XY:

0.461

AC XY:

34297

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.605

AC:

25088

AN:

41498

American (AMR)

AF:

0.400

AC:

6125

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1486

AN:

3472

East Asian (EAS)

AF:

0.198

AC:

1027

AN:

5192

South Asian (SAS)

AF:

0.451

AC:

2177

AN:

4828

European-Finnish (FIN)

AF:

0.410

AC:

4337

AN:

10580

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28896

AN:

67976

Other (OTH)

AF:

0.469

AC:

990

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1866

3732

5599

7465

9331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.440

Hom.:

8532

Bravo

AF:

0.471

Asia WGS

AF:

0.366

AC:

1274

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.033

(source)

DANN

Benign

0.73

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over