9-77728671-GAAAAA-GAAAAAAAA

Variant names:

• chr9-77728671-G-GAAA
• rs5898555
• NM_002072.5:c.736-7_736-5dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002072.5(GNAQ):​c.736-7_736-5dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,324,570 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00078 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 5 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	NM_002072.5	MANE Select	c.736-7_736-5dupTTT		splice_region intron	N/A	NP_002063.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	ENST00000286548.9	TSL:1 MANE Select	c.736-7_736-5dupTTT		splice_region intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.811-7_811-5dupTTT		splice_region intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.736-7_736-5dupTTT		splice_region intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145630 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.000115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000339 AC: 58 AN: 170990 AF XY: 0.000340

Gnomad AFR exome AF: 0.0000811

Gnomad AMR exome AF: 0.000650

Gnomad ASJ exome AF: 0.000339

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.000147

Gnomad NFE exome AF: 0.000350

Gnomad OTH exome AF: 0.000263

GnomAD4 exome AF: 0.000778 AC: 917 AN: 1178940 Hom.: 0 Cov.: 22 AF XY: 0.000700 AC XY: 414 AN XY: 591518

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000483 AC: 13 AN: 26942

American (AMR) AF: 0.000478 AC: 14 AN: 29302

Ashkenazi Jewish (ASJ) AF: 0.000188 AC: 4 AN: 21254

East Asian (EAS) AF: 0.000191 AC: 7 AN: 36576

South Asian (SAS) AF: 0.000498 AC: 35 AN: 70322

European-Finnish (FIN) AF: 0.000327 AC: 14 AN: 42850

Middle Eastern (MID) AF: 0.000440 AC: 2 AN: 4546

European-Non Finnish (NFE) AF: 0.000888 AC: 797 AN: 897340

Other (OTH) AF: 0.000622 AC: 31 AN: 49808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000687 AC: 1 AN: 145630 Hom.: 0 Cov.: 0 AF XY: 0.0000142 AC XY: 1 AN XY: 70540

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39516

American (AMR) AF: 0.00 AC: 0 AN: 14682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 4946

South Asian (SAS) AF: 0.00 AC: 0 AN: 4638

European-Finnish (FIN) AF: 0.000115 AC: 1 AN: 8730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66500

Other (OTH) AF: 0.00 AC: 0 AN: 1990

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5898555; hg19: chr9-80343587;