16-56343836-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138736.3(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
NM_138736.3 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 2.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNAO1NM_020988.3 linkc.723+6976A>G intron_variant Intron 6 of 8 ENST00000262493.12 NP_066268.1 P09471-1Q8N6I9B3KP89
GNAO1NM_138736.3 linkc.951A>G p.Lys317Lys synonymous_variant Exon 8 of 8 NP_620073.2 P09471-2Q8N6I9B3KP89Q6AWC5
GNAO1XM_011523003.4 linkc.597+6976A>G intron_variant Intron 6 of 8 XP_011521305.1
GNAO1XR_007064866.1 linkn.1698A>G non_coding_transcript_exon_variant Exon 8 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNAO1ENST00000262493.12 linkc.723+6976A>G intron_variant Intron 6 of 8 1 NM_020988.3 ENSP00000262493.6 P09471-1

Frequencies

GnomAD3 genomes
AF:
0.465
AC:
55766
AN:
119914
Hom.:
9114
Cov.:
28
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
GnomAD3 exomes
AF:
0.345
AC:
86379
AN:
250710
Hom.:
16095
AF XY:
0.348
AC XY:
47128
AN XY:
135568
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 SAS exome
AF:
0.463
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.:
34
AF XY:
0.364
AC XY:
264269
AN XY:
726440
show subpopulations
Gnomad4 AFR exome
AF:
0.581
Gnomad4 AMR exome
AF:
0.250
Gnomad4 ASJ exome
AF:
0.291
Gnomad4 EAS exome
AF:
0.210
Gnomad4 SAS exome
AF:
0.454
Gnomad4 FIN exome
AF:
0.271
Gnomad4 NFE exome
AF:
0.366
Gnomad4 OTH exome
AF:
0.362
GnomAD4 genome
AF:
0.465
AC:
55826
AN:
120018
Hom.:
9136
Cov.:
28
AF XY:
0.461
AC XY:
26876
AN XY:
58342
show subpopulations
Gnomad4 AFR
AF:
0.587
Gnomad4 AMR
AF:
0.367
Gnomad4 ASJ
AF:
0.383
Gnomad4 EAS
AF:
0.308
Gnomad4 SAS
AF:
0.508
Gnomad4 FIN
AF:
0.332
Gnomad4 NFE
AF:
0.434
Gnomad4 OTH
AF:
0.416
Alfa
AF:
0.362
Hom.:
14274
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
-
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

- -

Jul 15, 2018
GeneDx
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 v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
18
DANN
Benign
0.64

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: rs1799917; hg19: chr16-56377748; COSMIC: COSV52613707; API