1-109548660-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006496.4(GNAI3):c.-61C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.535

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 -14 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 id is 1262343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI3	NM_006496.4	c.-61C>T		5_prime_UTR_variant	1/9	ENST00000369851.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI3	ENST00000369851.7	c.-61C>T		5_prime_UTR_variant	1/9	1	NM_006496.4	P1

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

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0623

Gnomad4 ASJ exome AF: 0.0627

Gnomad4 EAS exome AF: 0.0171

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0512

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0999

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

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.0182

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0482

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.0597 Hom.: 57

Bravo AF: 0.110

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	6.2
Dann	Benign	0.78
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

Publications

LitVar

Other links and lift over

dbSNP: rs1279195; hg19: chr1-110091282; COSMIC: COSV63983667; COSMIC: COSV63983667;