7-2843920-T-C

Position:

• chr7-2843920-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2 PP3_Moderate BS2

The NM_007353.3(GNA12):​c.242A>G​(p.His81Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000348 in 1,438,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: GNA12 NM_007353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3	c.242A>G	p.His81Arg	missense_variant	1/4	ENST00000275364.8
GNA12	NM_001293092.2	c.242A>G	p.His81Arg	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8	c.242A>G	p.His81Arg	missense_variant	1/4	1	NM_007353.3	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1438196 Hom.: 0 Cov.: 31 AF XY: 0.00000559 AC XY: 4 AN XY: 714964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.76	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	4.1	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.90	P
Vest4		0.38
MutPred		0.86		Gain of sheet (P = 0.0125);
MVP		0.91
MPC		1.5
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.94
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2883554;