NM_020988.3:c.878-1490T>C

Variant names:

• chr16-56353376-T-C
• rs899228
• NM_020988.3:c.878-1490T>C

Variant summary

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

The NM_020988.3(GNAO1):​c.878-1490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,154 control chromosomes in the GnomAD database, including 8,233 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 0.30 (8231 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 8 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• genetic developmental and epileptic encephalopathy

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

ENSG00000272372 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	NM_020988.3	MANE Select	c.878-1490T>C		intron	N/A	NP_066268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.878-1490T>C		intron	N/A	ENSP00000262493.6
	GNAO1	ENST00000638705.1	TSL:1	c.878-1490T>C		intron	N/A	ENSP00000491223.1
	ENSG00000272372	ENST00000606772.1	TSL:6	n.149A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45586 AN: 151974 Hom.: 8219 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.226 AC: 14 AN: 62 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 13 AN XY: 52

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.205 AC: 9 AN: 44

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.300 AC: 45636 AN: 152092 Hom.: 8231 Cov.: 33 AF XY: 0.298 AC XY: 22157 AN XY: 74348

African (AFR) AF: 0.491 AC: 20334 AN: 41450

American (AMR) AF: 0.250 AC: 3827 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2046 AN: 5146

South Asian (SAS) AF: 0.372 AC: 1795 AN: 4824

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10608

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14358 AN: 67986

Other (OTH) AF: 0.274 AC: 578 AN: 2112

Alfa AF: 0.255 Hom.: 12001

Bravo AF: 0.316

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.62
PhyloP100		-0.99
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: rs899228; hg19: chr16-56387288;