9-77794429-A-G

Variant summary

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

The NM_002072.5(GNAQ):c.735+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,438,706 control chromosomes in the GnomAD database, including 207,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (16258 hom., cov: 31)
  • Exomes 𝑓: 0.53 (190778 hom.)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605

Genes affected

GNAQ (HGNC:4390): (G protein subunit alpha q) This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-77794429-A-G is Benign according to our data. Variant chr9-77794429-A-G is described in ClinVar as [Benign]. Clinvar id is 1234387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAQ	NM_002072.5	c.735+34T>C		intron_variant		ENST00000286548.9
GNAQ	XM_047423239.1	c.561+34T>C		intron_variant
GNAQ	XM_047423240.1	c.561+34T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAQ	ENST00000286548.9	c.735+34T>C		intron_variant		1	NM_002072.5	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64389 AN: 151826 Hom.: 16260 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.451

GnomAD3 exomes AF: 0.481 AC: 105929 AN: 220078 Hom.: 27498 AF XY: 0.492 AC XY: 58664 AN XY: 119286

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.534 AC: 686926 AN: 1286762 Hom.: 190778 Cov.: 16 AF XY: 0.533 AC XY: 343038 AN XY: 643084

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.424 AC: 64381 AN: 151944 Hom.: 16258 Cov.: 31 AF XY: 0.419 AC XY: 31122 AN XY: 74258

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.448

Alfa AF: 0.527 Hom.: 17626

Bravo AF: 0.409

Asia WGS AF: 0.307 AC: 1072 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	-0.77
Cadd	Benign	11
Dann	Benign	0.72

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: rs1328529; hg19: chr9-80409345; COSMIC: COSV54105959; COSMIC: COSV54105959;