rs144771965

Variant names:

• chr16-56334738-C-A
• NM_020988.3:c.474C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56334738-C-A
• chr16-56334738-C-G
• chr16-56334738-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_020988.3(GNAO1):​c.474C>A​(p.Asp158Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GNAO1 NM_020988.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the GNAO1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 70 curated pathogenic missense variants (we use a threshold of 10). The gene has 43 curated benign missense variants. Gene score misZ: 3.1919 (above the threshold of 3.09). Trascript score misZ: 4.549 (above the threshold of 3.09). GenCC associations: The gene is linked to developmental and epileptic encephalopathy, 17, neurodevelopmental disorder with involuntary movements, developmental and epileptic encephalopathy, movement disorder.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.474C>A	p.Asp158Glu	missense_variant	Exon 5 of 9	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.474C>A	p.Asp158Glu	missense_variant	Exon 5 of 8		NP_620073.2
GNAO1	XM_011523003.4	c.348C>A	p.Asp116Glu	missense_variant	Exon 5 of 9		XP_011521305.1
GNAO1	XR_007064866.1	n.1221C>A		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	c.474C>A	p.Asp158Glu	missense_variant	Exon 5 of 9	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;.;D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	1.4	L;L;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	N;.;N;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.018	D;.;D;D
Sift4G	Benign	0.24	T;.;T;.
Polyphen		0.96	D;D;D;.
Vest4		0.55
MutPred		0.60		Gain of ubiquitination at K154 (P = 0.1103);Gain of ubiquitination at K154 (P = 0.1103);Gain of ubiquitination at K154 (P = 0.1103);.;
MVP		0.73
MPC		2.4
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.51
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-56368650;