9-77728671-GAA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002072.5(GNAQ):c.736-6_736-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,324,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00057 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.572

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 9-77728671-GAA-G is Benign according to our data. Variant chr9-77728671-GAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-77728671-GAA-G is described in Lovd as [Likely_benign]. Variant chr9-77728671-GAA-G is described in Lovd as [Benign].
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAQ	NM_002072.5	c.736-6_736-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286548.9
GNAQ	XM_047423239.1	c.562-6_562-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
GNAQ	XM_047423240.1	c.562-6_562-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAQ	ENST00000286548.9	c.736-6_736-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002072.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000618 AC: 9 AN: 145624 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000568 AC: 669 AN: 1178350 Hom.: 0 AF XY: 0.000578 AC XY: 342 AN XY: 591254

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.000478

Gnomad4 ASJ exome AF: 0.000188

Gnomad4 EAS exome AF: 0.000412

Gnomad4 SAS exome AF: 0.000570

Gnomad4 FIN exome AF: 0.000842

Gnomad4 NFE exome AF: 0.000525

Gnomad4 OTH exome AF: 0.000642

GnomAD4 genome AF: 0.0000549 AC: 8 AN: 145690 Hom.: 0 Cov.: 0 AF XY: 0.0000708 AC XY: 5 AN XY: 70618

Gnomad4 AFR AF: 0.000177

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000217

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GNAQ-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs5898555; hg19: chr9-80343587;