7-80135244-G-C

Position:

• chr7-80135244-G-C

Variant summary

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

The NM_002069.6(GNAI1):​c.84G>C​(p.Glu28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,574 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GNAI1 NM_002069.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

Genes affected

GNAI1 (HGNC:4384): (G protein subunit alpha i1) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The alpha subunit binds guanine nucleotide, can hydrolyze GTP, and can interact with other proteins. The protein encoded by this gene represents the alpha subunit of an inhibitory complex. The encoded protein is part of a complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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=0.38622677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI1	NM_002069.6	c.84G>C	p.Glu28Asp	missense_variant	1/8	ENST00000649796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI1	ENST00000649796.2	c.84G>C	p.Glu28Asp	missense_variant	1/8		NM_002069.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384574 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 687298

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: 9.31e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.65	D
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.1	L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.88	D
Polyphen		0.0	B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;.
Vest4		0.15
MutPred		0.35		Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);
MVP		0.69
MPC		0.84
ClinPred		0.71	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.47

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: chr7-79764560;