rs559479

chr1-109595914-T-Achr1-109595914-T-C

Variant summary

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

The NM_006496.4(GNAI3):c.*3592T>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 0.419 in 151,934 control chromosomes in the GnomAD database, including 15,655 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 0.42 (15655 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: GNAI3 NM_006496.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI3	NM_006496.4	c.*3592T>A		3_prime_UTR_variant	9/9	ENST00000369851.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI3	ENST00000369851.7	c.*3592T>A		3_prime_UTR_variant	9/9	1	NM_006496.4	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63626 AN: 151816 Hom.: 15630 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.383

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.419 AC: 63701 AN: 151934 Hom.: 15655 Cov.: 31 AF XY: 0.415 AC XY: 30848 AN XY: 74244

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.382

Alfa AF: 0.374 Hom.: 1485

Bravo AF: 0.430

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.2
Dann	Benign	0.83

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: rs559479; hg19: chr1-110138536;