16-56295255-G-T

Variant names:

• chr16-56295255-G-T
• rs3790095
• NM_020988.3:c.303+19183G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020988.3(GNAO1):​c.303+19183G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,046 control chromosomes in the GnomAD database, including 3,974 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3974 hom., cov: 32)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 5 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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)

ENSG00000287866 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020988.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	NM_020988.3	MANE Select	c.303+19183G>T		intron	N/A	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.303+19183G>T		intron	N/A	NP_620073.2	P09471-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.303+19183G>T		intron	N/A	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000262494.13	TSL:1	c.303+19183G>T		intron	N/A	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000638705.1	TSL:1	c.303+19183G>T		intron	N/A	ENSP00000491223.1	P09471-1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32676 AN: 151928 Hom.: 3966 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 32715 AN: 152046 Hom.: 3974 Cov.: 32 AF XY: 0.220 AC XY: 16309 AN XY: 74296

African (AFR) AF: 0.291 AC: 12040 AN: 41440

American (AMR) AF: 0.248 AC: 3787 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2123 AN: 5148

South Asian (SAS) AF: 0.109 AC: 525 AN: 4822

European-Finnish (FIN) AF: 0.247 AC: 2615 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10544 AN: 67986

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.161 Hom.: 1275

Bravo AF: 0.218

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3790095; hg19: chr16-56329167;