Variant 16-56192252-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5

The ENST00000262493.12(GNAO1):c.17G>T(p.Ser6Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNAO1
ENST00000262493.12 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.53

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 4.549 (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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.934

PP5

Variant 16-56192252-G-T is Pathogenic according to our data. Variant chr16-56192252-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1802165.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GNAO1	NM_020988.3 linkuse as main transcript	c.17G>T	p.Ser6Ile	missense_variant	1/9	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3 linkuse as main transcript	c.17G>T	p.Ser6Ile	missense_variant	1/8		NP_620073.2
GNAO1	XR_007064866.1 linkuse as main transcript	n.764G>T		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12 linkuse as main transcript	c.17G>T	p.Ser6Ile	missense_variant	1/9	1	NM_020988.3	ENSP00000262493	P1	P09471-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1444788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718652

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

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 17

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Key Laboratory of Neurobehavioral Science for Children, Children's Hospital Affiliated of Zhengzhou University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;.;D;.;T;.

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D

M_CAP

Pathogenic

0.61

MetaRNN

Pathogenic

0.93

D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.1

H;.;H;H;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-4.1

D;.;.;D;.;.

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

D;.;.;D;.;.

Sift4G

Pathogenic

0.0

D;.;.;D;D;.

Polyphen

1.0

D;.;D;D;.;.

Vest4

0.52

MutPred

0.76

Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);

MVP

0.90

MPC

2.9

ClinPred

1.0

GERP RS

4.8

Varity_R

0.93

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over