rs10487577

Positions:

• chr7-2770844-T-C

Variant summary

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

The NM_007353.3(GNA12):​c.525+24084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,310 control chromosomes in the GnomAD database, including 275 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 0.035 (275 hom., cov: 32)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA12	NM_007353.3	c.525+24084A>G		intron_variant		ENST00000275364.8	NP_031379.2
GNA12	NM_001282441.2	c.348+24084A>G		intron_variant			NP_001269370.1
GNA12	NM_001293092.2	c.525+24084A>G		intron_variant			NP_001280021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.525+24084A>G		intron_variant		1	NM_007353.3	ENSP00000275364	P1
GNA12	ENST00000407904.7	c.348+24084A>G		intron_variant		2		ENSP00000385935
AMZ1	ENST00000433945.1	n.333-4445T>C		intron_variant, non_coding_transcript_variant		4
GNA12	ENST00000471281.5	n.426+23876A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5293 AN: 152192 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0349 AC: 5321 AN: 152310 Hom.: 275 Cov.: 32 AF XY: 0.0344 AC XY: 2559 AN XY: 74484

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00772

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0188 Hom.: 19

Bravo AF: 0.0412

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.40

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: rs10487577; hg19: chr7-2810478;