1-109548660-C-A

Variant names:

• chr1-109548660-C-A
• rs1279195
• NM_006496.4:c.-61C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006496.4(GNAI3):​c.-61C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,066,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: GNAI3 NM_006496.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 0 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

ENSG00000290117 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

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.-61C>A		5_prime_UTR	Exon 1 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.-61C>A		5_prime_UTR	Exon 1 of 9	ENSP00000358867.4	P08754
	GNAI3	ENST00000920644.1		c.-61C>A		5_prime_UTR	Exon 1 of 9	ENSP00000590703.1
	GNAI3	ENST00000879740.1		c.-61C>A		5_prime_UTR	Exon 1 of 8	ENSP00000549799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000375 AC: 4 AN: 1066452 Hom.: 0 Cov.: 14 AF XY: 0.00000369 AC XY: 2 AN XY: 542022

African (AFR) AF: 0.00 AC: 0 AN: 26006

American (AMR) AF: 0.00 AC: 0 AN: 40946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22742

East Asian (EAS) AF: 0.00 AC: 0 AN: 36954

South Asian (SAS) AF: 0.0000265 AC: 2 AN: 75548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3748

European-Non Finnish (NFE) AF: 0.00000262 AC: 2 AN: 762008

Other (OTH) AF: 0.00 AC: 0 AN: 46948

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		-0.54
PromoterAI		-0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs1279195; hg19: chr1-110091282;