rs559479

Variant names:

• chr1-109595914-T-A
• rs559479
• NM_006496.4:c.*3592T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109595914-T-A
• chr1-109595914-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GNAI3 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006496.4. 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
	GNAI3	NM_006496.4	MANE Select	c.*3592T>A		3_prime_UTR	Exon 9 of 9	NP_006487.1	P08754

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI3	ENST00000369851.7	TSL:1 MANE Select	c.*3592T>A		3_prime_UTR	Exon 9 of 9	ENSP00000358867.4	P08754
	GNAI3	ENST00000879740.1		c.*3681T>A		downstream_gene	N/A	ENSP00000549799.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.689 AC: 28520 AN: 41398

American (AMR) AF: 0.309 AC: 4716 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1856 AN: 5182

South Asian (SAS) AF: 0.483 AC: 2329 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2923 AN: 10526

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20904 AN: 67964

Other (OTH) AF: 0.382 AC: 802 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.83
PhyloP100		0.43

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

Other links and lift over

dbSNP: rs559479; hg19: chr1-110138536;