7-2843904-G-C

Position:

• chr7-2843904-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007353.3(GNA12):​c.258C>G​(p.Asp86Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,427,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GNA12 NM_007353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36236408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3	c.258C>G	p.Asp86Glu	missense_variant	1/4	ENST00000275364.8
GNA12	NM_001293092.2	c.258C>G	p.Asp86Glu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8	c.258C>G	p.Asp86Glu	missense_variant	1/4	1	NM_007353.3	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427610 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709538

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: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.258C>G (p.D86E) alteration is located in exon 1 (coding exon 1) of the GNA12 gene. This alteration results from a C to G substitution at nucleotide position 258, causing the aspartic acid (D) at amino acid position 86 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.32
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.0020	B
Vest4		0.34
MutPred		0.60		Gain of helix (P = 0.0496);
MVP		0.66
MPC		0.81
ClinPred		0.24	T
GERP RS		1.9
Varity_R		0.14
gMVP		0.44

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: chr7-2883538;