1-109592686-G-A

Position:

• chr1-109592686-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006496.4(GNAI3):​c.*364G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,872 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2542 hom., cov: 32)
  • Exomes 𝑓: 0.20 (19 hom.)
• Consequence: GNAI3 NM_006496.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

GNAI3 (HGNC:4387): (G protein subunit alpha i3) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI3	NM_006496.4	c.*364G>A		3_prime_UTR_variant	9/9	ENST00000369851.7	NP_006487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI3	ENST00000369851.7	c.*364G>A		3_prime_UTR_variant	9/9	1	NM_006496.4	ENSP00000358867	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26669 AN: 151822 Hom.: 2545 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.200 AC: 186 AN: 930 Hom.: 19 Cov.: 0 AF XY: 0.225 AC XY: 113 AN XY: 502

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.176 AC: 26683 AN: 151942 Hom.: 2542 Cov.: 32 AF XY: 0.179 AC XY: 13288 AN XY: 74250

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.185

Alfa AF: 0.166 Hom.: 2002

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.8
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs7371; hg19: chr1-110135308;