Genetic Variant GNAO1:p.Ala11Ala (chr16-56192268-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_020988.3(GNAO1):c.33C>T(p.Ala11Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,656 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GNAO1
NM_020988.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.449

Publications

0 publications found

Variant links:

Genes affected

GNAO1 (HGNC:4389): (G protein subunit alpha o1) The protein encoded by this gene represents the alpha subunit of the Go heterotrimeric G-protein signal-transducing complex. Defects in this gene are a cause of early-onset epileptic encephalopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

GNAO1 links:

GNAO1-DT (HGNC:27543): (GNAO1 divergent transcript)

GNAO1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 16-56192268-C-T is Benign according to our data. Variant chr16-56192268-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1594730.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.449 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020988.3. 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
	GNAO1	NM_020988.3	MANE Select	c.33C>T	p.Ala11Ala	synonymous	Exon 1 of 9	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.33C>T	p.Ala11Ala	synonymous	Exon 1 of 8	NP_620073.2	P09471-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.33C>T	p.Ala11Ala	synonymous	Exon 1 of 9	ENSP00000262493.6	P09471-1
GNAO1	ENST00000262494.13	TSL:1	c.33C>T	p.Ala11Ala	synonymous	Exon 1 of 8	ENSP00000262494.7	P09471-2
GNAO1	ENST00000638705.1	TSL:1	c.33C>T	p.Ala11Ala	synonymous	Exon 1 of 8	ENSP00000491223.1	P09471-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455528

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108420

Other (OTH)

AF:

0.00

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.45

PromoterAI

-0.078

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over