7-2731301-GC-AT

Variant names:

• chr7-2731301-GC-AT
• NM_007353.3:c.1025_1026delGCinsAT
• GNA12 p.Arg342His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_007353.3(GNA12):​c.1025_1026delGCinsAT​(p.Arg342His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R342L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNA12 NM_007353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74
• 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]

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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1025_1026delGCinsAT	p.Arg342His	missense	N/A	NP_031379.2
	GNA12	NM_001293092.2		c.974_975delGCinsAT	p.Arg325His	missense	N/A	NP_001280021.1
	GNA12	NM_001282441.2		c.848_849delGCinsAT	p.Arg283His	missense	N/A	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.1025_1026delGCinsAT	p.Arg342His	missense	N/A	ENSP00000275364.3	Q03113-1
	AMZ1	ENST00000489665.1	TSL:1	n.550+21485_550+21486delGCinsAT		intron	N/A
	GNA12	ENST00000954395.1		c.1103_1104delGCinsAT	p.Arg368His	missense	N/A	ENSP00000624454.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-2770935;