chr16-56334777-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020988.3(GNAO1):c.513C>T(p.Thr171Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,613,306 control chromosomes in the GnomAD database, including 136,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14308 hom., cov: 34)

Exomes 𝑓: 0.40 ( 122114 hom. )

Consequence

GNAO1
NM_020988.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.914

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 16-56334777-C-T is Benign according to our data. Variant chr16-56334777-C-T is described in ClinVar as [Benign]. Clinvar id is 585942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.914 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3 link	c.513C>T	p.Thr171Thr	synonymous_variant	Exon 5 of 9	ENST00000262493.12	NP_066268.1	P09471-1Q8N6I9B3KP89
GNAO1	NM_138736.3 link	c.513C>T	p.Thr171Thr	synonymous_variant	Exon 5 of 8		NP_620073.2	P09471-2Q8N6I9B3KP89Q6AWC5
GNAO1	XM_011523003.4 link	c.387C>T	p.Thr129Thr	synonymous_variant	Exon 5 of 9		XP_011521305.1
GNAO1	XR_007064866.1 link	n.1260C>T		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12 link	c.513C>T	p.Thr171Thr	synonymous_variant	Exon 5 of 9	1	NM_020988.3	ENSP00000262493.6		P09471-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64632

AN:

152010

Hom.:

14285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.444

AC:

111505

AN:

251174

Hom.:

26172

AF XY:

0.437

AC XY:

59325

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.515

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.758

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.402

AC:

587225

AN:

1461178

Hom.:

122114

Cov.:

AF XY:

0.401

AC XY:

291271

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.404

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.776

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.480

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.425

AC:

64702

AN:

152128

Hom.:

14308

Cov.:

AF XY:

0.434

AC XY:

32245

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.411

Gnomad4 AMR

AF:

0.497

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.391

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.401

Hom.:

19354

Bravo

AF:

0.428

Asia WGS

AF:

0.583

AC:

2028

AN:

3478

EpiCase

AF:

0.398

EpiControl

AF:

0.403

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 78% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 73. Only high quality variants are reported. -

Inborn genetic diseases

Benign:1

Feb 09, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 17

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurodevelopmental disorder with involuntary movements

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.3

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over