16-56343836-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000262494.13(GNAO1):c.951A>G(p.Lys317Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,580,160 control chromosomes in the GnomAD database, including 108,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 9136 hom., cov: 28)

Exomes 𝑓: 0.36 ( 99337 hom. )

Consequence

GNAO1
ENST00000262494.13 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.93

Publications

28 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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 17
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
movement disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
neurodevelopmental disorder with involuntary movements
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GNAO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 16-56343836-A-G is Benign according to our data. Variant chr16-56343836-A-G is described in ClinVar as Benign. ClinVar VariationId is 585945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262494.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	NM_020988.3	MANE Select	c.723+6976A>G		intron	N/A	NP_066268.1
	GNAO1	NM_138736.3		c.951A>G	p.Lys317Lys	synonymous	Exon 8 of 8	NP_620073.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GNAO1	ENST00000262494.13	TSL:1	c.951A>G	p.Lys317Lys	synonymous	Exon 8 of 8	ENSP00000262494.7
GNAO1	ENST00000564798.2	TSL:1	n.766A>G		non_coding_transcript_exon	Exon 2 of 2
GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.723+6976A>G		intron	N/A	ENSP00000262493.6

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

55766

AN:

119914

Hom.:

9114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.345

AC:

86379

AN:

250710

AF XY:

0.348

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.363

AC:

530211

AN:

1460142

Hom.:

99337

Cov.:

AF XY:

0.364

AC XY:

264269

AN XY:

726440

show subpopulations

African (AFR)

AF:

0.581

AC:

19419

AN:

33436

American (AMR)

AF:

0.250

AC:

11183

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

7607

AN:

26100

East Asian (EAS)

AF:

0.210

AC:

8313

AN:

39612

South Asian (SAS)

AF:

0.454

AC:

39080

AN:

86164

European-Finnish (FIN)

AF:

0.271

AC:

14469

AN:

53298

Middle Eastern (MID)

AF:

0.298

AC:

1715

AN:

5762

European-Non Finnish (NFE)

AF:

0.366

AC:

406570

AN:

1110794

Other (OTH)

AF:

0.362

AC:

21855

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16962

33924

50885

67847

84809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12992

25984

38976

51968

64960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.465

AC:

55826

AN:

120018

Hom.:

9136

Cov.:

AF XY:

0.461

AC XY:

26876

AN XY:

58342

show subpopulations

African (AFR)

AF:

0.587

AC:

21314

AN:

36326

American (AMR)

AF:

0.367

AC:

3966

AN:

10812

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

953

AN:

2488

East Asian (EAS)

AF:

0.308

AC:

1045

AN:

3388

South Asian (SAS)

AF:

0.508

AC:

2038

AN:

4014

European-Finnish (FIN)

AF:

0.332

AC:

2684

AN:

8086

Middle Eastern (MID)

AF:

0.404

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.434

AC:

22744

AN:

52410

Other (OTH)

AF:

0.416

AC:

662

AN:

1590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

1716

3433

5149

6866

8582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.364

Hom.:

16571

Bravo

AF:

0.406

EpiCase

AF:

0.346

EpiControl

AF:

0.342

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

2.9

Mutation Taster

=79/21

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over