chr16-56336791-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020988.3(GNAO1):​c.654C>T​(p.Asp218Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,613,736 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 34)
Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

GNAO1
NM_020988.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.115

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 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 16-56336791-C-T is Benign according to our data. Variant chr16-56336791-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.115 with no splicing effect.
BS2
High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNAO1NM_020988.3 linkc.654C>T p.Asp218Asp synonymous_variant Exon 6 of 9 ENST00000262493.12 NP_066268.1 P09471-1Q8N6I9B3KP89
GNAO1NM_138736.3 linkc.654C>T p.Asp218Asp synonymous_variant Exon 6 of 8 NP_620073.2 P09471-2Q8N6I9B3KP89Q6AWC5
GNAO1XM_011523003.4 linkc.528C>T p.Asp176Asp synonymous_variant Exon 6 of 9 XP_011521305.1
GNAO1XR_007064866.1 linkn.1401C>T non_coding_transcript_exon_variant Exon 6 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNAO1ENST00000262493.12 linkc.654C>T p.Asp218Asp synonymous_variant Exon 6 of 9 1 NM_020988.3 ENSP00000262493.6 P09471-1

Frequencies

GnomAD3 genomes
AF:
0.00189
AC:
288
AN:
152266
Hom.:
2
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00649
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
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:
0.0000294
Gnomad OTH
AF:
0.00239
GnomAD2 exomes
AF:
0.000503
AC:
126
AN:
250518
AF XY:
0.000310
show subpopulations
Gnomad AFR exome
AF:
0.00724
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000163
AC:
238
AN:
1461352
Hom.:
2
Cov.:
31
AF XY:
0.000131
AC XY:
95
AN XY:
727026
show subpopulations
African (AFR)
AF:
0.00597
AC:
200
AN:
33476
American (AMR)
AF:
0.000246
AC:
11
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53058
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000719
AC:
8
AN:
1111888
Other (OTH)
AF:
0.000298
AC:
18
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
12
25
37
50
62
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00192
AC:
292
AN:
152384
Hom.:
2
Cov.:
34
AF XY:
0.00189
AC XY:
141
AN XY:
74522
show subpopulations
African (AFR)
AF:
0.00656
AC:
273
AN:
41592
American (AMR)
AF:
0.000784
AC:
12
AN:
15314
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68040
Other (OTH)
AF:
0.00237
AC:
5
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
14
27
41
54
68
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<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:
0.00111
Hom.:
0
Bravo
AF:
0.00216
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jan 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

GNAO1: BP4, BP7, BS2 -

Nov 06, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Inborn genetic diseases Benign:1
Jun 18, 2016
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely 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. -

Developmental and epileptic encephalopathy Benign:1
Jan 19, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.35
CADD
Benign
14
DANN
Benign
0.84
PhyloP100
0.12
PromoterAI
-0.14
Neutral
Mutation Taster
=99/1
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

Other links and lift over

dbSNP: rs139322464; hg19: chr16-56370703; COSMIC: COSV52617166; COSMIC: COSV52617166; API