7-2795026-C-T

Variant names:

• chr7-2795026-C-T
• rs1210452556
• NM_007353.3:c.427G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007353.3(GNA12):​c.427G>A​(p.Glu143Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E143Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNA12 NM_007353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	NM_007353.3	MANE Select	c.427G>A	p.Glu143Lys	missense	Exon 2 of 4	NP_031379.2
	GNA12	NM_001293092.2		c.427G>A	p.Glu143Lys	missense	Exon 2 of 3	NP_001280021.1
	GNA12	NM_001282441.2		c.250G>A	p.Glu84Lys	missense	Exon 3 of 5	NP_001269370.1	Q03113-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	ENST00000275364.8	TSL:1 MANE Select	c.427G>A	p.Glu143Lys	missense	Exon 2 of 4	ENSP00000275364.3	Q03113-1
	GNA12	ENST00000954395.1		c.505G>A	p.Glu169Lys	missense	Exon 3 of 5	ENSP00000624454.1
	GNA12	ENST00000917992.1		c.478G>A	p.Glu160Lys	missense	Exon 3 of 5	ENSP00000588051.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.9	L
PhyloP100		7.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N
REVEL	Pathogenic	0.75
Sift	Benign	0.054	T
Sift4G	Benign	0.092	T
Polyphen		0.94	P
Vest4		0.64
MutPred		0.58		Gain of methylation at E143 (P = 0.0166)
MVP		0.88
MPC		1.2
ClinPred		0.83	D
GERP RS		5.6
Varity_R		0.33
gMVP		0.79
Mutation Taster		=24/76	disease causing

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: rs1210452556; hg19: chr7-2834660;