rs798527

Variant names:

• chr7-2733156-T-C
• rs798527
• NM_007353.3:c.576+295A>G

Variant summary

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

The NM_007353.3(GNA12):​c.576+295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,010 control chromosomes in the GnomAD database, including 26,113 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 0.58 (26113 hom., cov: 31)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA12	NM_007353.3	c.576+295A>G		intron_variant	Intron 3 of 3	ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.576+295A>G		intron_variant	Intron 3 of 3	1	NM_007353.3	ENSP00000275364.3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88544 AN: 151892 Hom.: 26089 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.583 AC: 88610 AN: 152010 Hom.: 26113 Cov.: 31 AF XY: 0.578 AC XY: 42926 AN XY: 74284

African (AFR) AF: 0.519 AC: 21492 AN: 41434

American (AMR) AF: 0.632 AC: 9656 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1885 AN: 5160

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4816

European-Finnish (FIN) AF: 0.589 AC: 6218 AN: 10556

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42938 AN: 67982

Other (OTH) AF: 0.584 AC: 1231 AN: 2108

Alfa AF: 0.617 Hom.: 16800

Bravo AF: 0.586

Asia WGS AF: 0.532 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		0.15
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: rs798527; hg19: chr7-2772790;