rs9332401

Positions:

• chr7-2775100-A-G

Variant summary

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

The NM_007353.3(GNA12):​c.525+19828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,240 control chromosomes in the GnomAD database, including 1,972 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 0.16 (1972 hom., cov: 32)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3	c.525+19828T>C		intron_variant		ENST00000275364.8
GNA12	NM_001282441.2	c.348+19828T>C		intron_variant
GNA12	NM_001293092.2	c.525+19828T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8	c.525+19828T>C		intron_variant		1	NM_007353.3	P1
GNA12	ENST00000407904.7	c.348+19828T>C		intron_variant		2
AMZ1	ENST00000433945.1	n.333-189A>G		intron_variant, non_coding_transcript_variant		4
GNA12	ENST00000471281.5	n.426+19620T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23820 AN: 152122 Hom.: 1968 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.157 AC: 23835 AN: 152240 Hom.: 1972 Cov.: 32 AF XY: 0.153 AC XY: 11399 AN XY: 74454

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.159

Alfa AF: 0.186 Hom.: 5546

Bravo AF: 0.160

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.36

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: rs9332401; hg19: chr7-2814734;