7-2728927-C-T

Position:

• chr7-2728927-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GNA12	NM_007353.3	c.*2254G>A		3_prime_UTR_variant	4/4	ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.*2254G>A		3_prime_UTR_variant	4/4	1	NM_007353.3	ENSP00000275364	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70663 AN: 152044 Hom.: 17192 Cov.: 33

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: 55 AN: 144 Hom.: 10 Cov.: 0 AF XY: 0.378 AC XY: 28 AN XY: 74

Gnomad4 EAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.465 AC: 70744 AN: 152162 Hom.: 17224 Cov.: 33 AF XY: 0.461 AC XY: 34297 AN XY: 74388

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.469

Alfa AF: 0.437 Hom.: 5244

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
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs11354; hg19: chr7-2768561;