7-2756323-A-G

Variant names:

• chr7-2756323-A-G
• rs798497
• NM_007353.3:c.526-22822T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007353.3(GNA12):​c.526-22822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,146 control chromosomes in the GnomAD database, including 5,301 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 0.25 (5301 hom., cov: 33)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 58 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	NM_007353.3	MANE Select	c.526-22822T>C		intron	N/A	NP_031379.2
	GNA12	NM_001293092.2		c.526-24573T>C		intron	N/A	NP_001280021.1
	AMZ1	NM_001321766.2		c.949-8389A>G		intron	N/A	NP_001308695.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	ENST00000275364.8	TSL:1 MANE Select	c.526-22822T>C		intron	N/A	ENSP00000275364.3
	AMZ1	ENST00000489665.1	TSL:1	n.551-8389A>G		intron	N/A
	GNA12	ENST00000407904.7	TSL:2	c.349-22822T>C		intron	N/A	ENSP00000385935.3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37978 AN: 152028 Hom.: 5293 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 38010 AN: 152146 Hom.: 5301 Cov.: 33 AF XY: 0.253 AC XY: 18823 AN XY: 74374

African (AFR) AF: 0.141 AC: 5837 AN: 41504

American (AMR) AF: 0.285 AC: 4359 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5188

South Asian (SAS) AF: 0.166 AC: 800 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4043 AN: 10546

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20006 AN: 68004

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.278 Hom.: 22000

Bravo AF: 0.239

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.85
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs798497; hg19: chr7-2795957;