chr9-77728671-GAAAA-G

Variant names:

• chr9-77728671-GAAAA-G
• rs5898555
• NM_002072.5:c.736-8_736-5delTTTT

Variant summary

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

The NM_002072.5(GNAQ):​c.736-8_736-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000592 in 1,183,112 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAQ	NM_002072.5	c.736-8_736-5delTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000286548.9	NP_002063.2
GNAQ	XM_047423239.1	c.562-8_562-5delTTTT		splice_region_variant, intron_variant	Intron 5 of 6		XP_047279195.1
GNAQ	XM_047423240.1	c.562-8_562-5delTTTT		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.736-8_736-5delTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_002072.5	ENSP00000286548.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000592 AC: 7 AN: 1183112 Hom.: 0 AF XY: 0.00000505 AC XY: 3 AN XY: 593592

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

African (AFR) AF: 0.00 AC: 0 AN: 26996

American (AMR) AF: 0.00 AC: 0 AN: 29394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21322

East Asian (EAS) AF: 0.00 AC: 0 AN: 36624

South Asian (SAS) AF: 0.00 AC: 0 AN: 70578

European-Finnish (FIN) AF: 0.0000466 AC: 2 AN: 42918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00000444 AC: 4 AN: 900720

Other (OTH) AF: 0.0000200 AC: 1 AN: 50000

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=96/4	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: rs5898555; hg19: chr9-80343587;