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GeneBe

9-77728638-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002072.5(GNAQ):c.765T>C(p.Phe255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,608,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

GNAQ
NM_002072.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-77728638-A-G is Benign according to our data. Variant chr9-77728638-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1592446.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.07 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 38 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GNAQNM_002072.5 linkuse as main transcriptc.765T>C p.Phe255= synonymous_variant 6/7 ENST00000286548.9
GNAQXM_047423239.1 linkuse as main transcriptc.591T>C p.Phe197= synonymous_variant 6/7
GNAQXM_047423240.1 linkuse as main transcriptc.591T>C p.Phe197= synonymous_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GNAQENST00000286548.9 linkuse as main transcriptc.765T>C p.Phe255= synonymous_variant 6/71 NM_002072.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000251
AC:
38
AN:
151546
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000971
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
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:
0.000456
Gnomad OTH
AF:
0.000483
GnomAD3 exomes
AF:
0.000303
AC:
76
AN:
250978
Hom.:
0
AF XY:
0.000324
AC XY:
44
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000493
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000484
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000500
AC:
728
AN:
1457232
Hom.:
0
Cov.:
28
AF XY:
0.000466
AC XY:
338
AN XY:
725290
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000612
Gnomad4 OTH exome
AF:
0.000415
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000251
AC:
38
AN:
151546
Hom.:
0
Cov.:
32
AF XY:
0.000270
AC XY:
20
AN XY:
73988
show subpopulations
Gnomad4 AFR
AF:
0.0000971
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.000483
Alfa
AF:
0.000411
Hom.:
0
Bravo
AF:
0.000446
EpiCase
AF:
0.000600
EpiControl
AF:
0.000296

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeOct 27, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
11
Dann
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144682617; hg19: chr9-80343554; API