rs1279195

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-109548660-C-T
• chr1-109548660-C-A
• chr1-109548660-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006496.4(GNAI3):​c.-61C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 1,217,582 control chromosomes in the GnomAD database, including 6,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (930 hom., cov: 32)
  • Exomes 𝑓: 0.099 (5728 hom.)
• Consequence: GNAI3 NM_006496.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.535
• Publications: 13 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-109548660-C-T is Benign according to our data. Variant chr1-109548660-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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.-61C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_006487.1	P08754
	GNAI3	NM_006496.4	MANE Select	c.-61C>T		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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000358867.4	P08754
	GNAI3	ENST00000369851.7	TSL:1 MANE Select	c.-61C>T		5_prime_UTR	Exon 1 of 9	ENSP00000358867.4	P08754
	GNAI3	ENST00000920644.1		c.-61C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000590703.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16078 AN: 152056 Hom.: 932 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0987

GnomAD4 exome AF: 0.0989 AC: 105348 AN: 1065410 Hom.: 5728 Cov.: 14 AF XY: 0.0994 AC XY: 53842 AN XY: 541504

African (AFR) AF: 0.156 AC: 4049 AN: 25950

American (AMR) AF: 0.0623 AC: 2550 AN: 40932

Ashkenazi Jewish (ASJ) AF: 0.0627 AC: 1426 AN: 22732

East Asian (EAS) AF: 0.0171 AC: 631 AN: 36948

South Asian (SAS) AF: 0.115 AC: 8647 AN: 75490

European-Finnish (FIN) AF: 0.0512 AC: 2637 AN: 51550

Middle Eastern (MID) AF: 0.105 AC: 392 AN: 3746

European-Non Finnish (NFE) AF: 0.106 AC: 80331 AN: 761164

Other (OTH) AF: 0.0999 AC: 4685 AN: 46898

GnomAD4 genome AF: 0.106 AC: 16081 AN: 152172 Hom.: 930 Cov.: 32 AF XY: 0.102 AC XY: 7624 AN XY: 74386

African (AFR) AF: 0.151 AC: 6278 AN: 41520

American (AMR) AF: 0.0816 AC: 1248 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 217 AN: 3468

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5176

South Asian (SAS) AF: 0.126 AC: 609 AN: 4824

European-Finnish (FIN) AF: 0.0482 AC: 511 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0991 AC: 6735 AN: 67974

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0627 Hom.: 67

Bravo AF: 0.110

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		-0.54
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV63983667; COSMIC: COSV63983667;