Variant rs1799917 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BS1BS2

The ENST00000262494.13(GNAO1):c.951A>C(p.Lys317Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 111,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K317R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.018 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNAO1
ENST00000262494.13 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

GNAO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GNAO1. . Gene score misZ 3.1919 (greater than the threshold 3.09). Trascript score misZ 3.4487 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 17, neurodevelopmental disorder with involuntary movements, developmental and epileptic encephalopathy, movement disorder.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0176 (1962/111198) while in subpopulation EAS AF= 0.0221 (71/3208). AF 95% confidence interval is 0.0204. There are 0 homozygotes in gnomad4. There are 896 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1962 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNAO1	NM_020988.3 linkuse as main transcript	c.723+6976A>C		intron_variant		ENST00000262493.12
GNAO1	NM_138736.3 linkuse as main transcript	c.951A>C	p.Lys317Asn	missense_variant	8/8
GNAO1	XM_011523003.4 linkuse as main transcript	c.597+6976A>C		intron_variant
GNAO1	XR_007064866.1 linkuse as main transcript	n.1698A>C		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12 linkuse as main transcript	c.723+6976A>C		intron_variant		1	NM_020988.3	P1	P09471-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

1963

AN:

111088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.00456

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0191

Gnomad EAS

AF:

0.0220

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00990

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0206

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726380

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0176

AC:

1962

AN:

111198

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

896

AN XY:

54288

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0191

Gnomad4 EAS

AF:

0.0221

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00536

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.000140

Hom.:

14274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.50

MetaSVM

Pathogenic

0.98

MutationTaster

Benign

4.1e-10

P;P

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.76

MutPred

0.61

Loss of methylation at K317 (P = 0.0011);

MVP

0.71

MPC

1.1

ClinPred

0.99

GERP RS

4.4

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over