9-77728669-T-TG

Variant names:

• chr9-77728669-T-TG
• rs757232284
• NM_002072.5:c.736-3dupC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_002072.5(GNAQ):​c.736-3dupC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000165 in 1,457,866 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.49

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 9-77728669-T-TG is Benign according to our data. Variant chr9-77728669-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 3058149.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAQ	NM_002072.5	c.736-3dupC		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000286548.9	NP_002063.2
GNAQ	XM_047423239.1	c.562-3dupC		splice_region_variant, intron_variant	Intron 5 of 6		XP_047279195.1
GNAQ	XM_047423240.1	c.562-3dupC		splice_region_variant, intron_variant	Intron 5 of 6		XP_047279196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAQ	ENST00000286548.9	c.736-3_736-2insC		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_002072.5	ENSP00000286548.4

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 12 AN: 86358 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000288

Gnomad OTH AF: 0.000887

GnomAD2 exomes AF: 0.0000666 AC: 12 AN: 180240 AF XY: 0.0000605

Gnomad AFR exome AF: 0.000143

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 229 AN: 1371404 Hom.: 0 Cov.: 26 AF XY: 0.000164 AC XY: 112 AN XY: 683076

African (AFR) AF: 0.000201 AC: 6 AN: 29902

American (AMR) AF: 0.0000306 AC: 1 AN: 32694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23828

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38978

South Asian (SAS) AF: 0.0000514 AC: 4 AN: 77752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.000187 AC: 198 AN: 1056138

Other (OTH) AF: 0.000335 AC: 19 AN: 56674

GnomAD4 genome AF: 0.000139 AC: 12 AN: 86462 Hom.: 0 Cov.: 30 AF XY: 0.000189 AC XY: 8 AN XY: 42370

African (AFR) AF: 0.0000355 AC: 1 AN: 28190

American (AMR) AF: 0.00 AC: 0 AN: 7712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1972

East Asian (EAS) AF: 0.00 AC: 0 AN: 4072

South Asian (SAS) AF: 0.00 AC: 0 AN: 2872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.000288 AC: 10 AN: 34742

Other (OTH) AF: 0.000876 AC: 1 AN: 1142

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GNAQ-related disorder Benign:1

Apr 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=72/28	polymorphism

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

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Other links and lift over

dbSNP: rs757232284; hg19: chr9-80343585;