rs10512065

Variant names:

• chr9-78010728-G-A
• rs10512065
• NM_002072.5:c.136+20372C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002072.5(GNAQ):​c.136+20372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 151,902 control chromosomes in the GnomAD database, including 816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.089 (816 hom., cov: 32)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 6 publications found

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]

GNAQ Gene-Disease associations (from GenCC):

• congenital hemangioma

  Inheritance: AD Classification: STRONG Submitted by: G2P
• Sturge-Weber syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000307361 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAQ	NM_002072.5	c.136+20372C>T		intron_variant	Intron 1 of 6	ENST00000286548.9	NP_002063.2
GNAQ	XM_047423239.1	c.-39+20014C>T		intron_variant	Intron 1 of 6		XP_047279195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAQ	ENST00000286548.9	c.136+20372C>T		intron_variant	Intron 1 of 6	1	NM_002072.5	ENSP00000286548.4
GNAQ	ENST00000411677.1	c.49+19787C>T		intron_variant	Intron 1 of 3	3		ENSP00000391501.1
ENSG00000307361	ENST00000825387.1	n.161+20014C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13556 AN: 151784 Hom.: 814 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0893 AC: 13569 AN: 151902 Hom.: 816 Cov.: 32 AF XY: 0.0889 AC XY: 6603 AN XY: 74264

African (AFR) AF: 0.0221 AC: 915 AN: 41438

American (AMR) AF: 0.0888 AC: 1354 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3464

East Asian (EAS) AF: 0.221 AC: 1134 AN: 5126

South Asian (SAS) AF: 0.133 AC: 637 AN: 4806

European-Finnish (FIN) AF: 0.0622 AC: 658 AN: 10572

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8029 AN: 67936

Other (OTH) AF: 0.122 AC: 256 AN: 2106

Alfa AF: 0.107 Hom.: 606

Bravo AF: 0.0906

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.49
PhyloP100		-0.30
Mutation Taster		=100/0	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: rs10512065; hg19: chr9-80625644;