rs1799917

Variant names:

• chr16-56343836-A-G
• rs1799917
• ENST00000262494.13:c.951A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-56343836-A-G
• chr16-56343836-A-C
• chr16-56343836-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_138736.3(GNAO1):​c.951A>G​(p.Lys317Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,580,160 control chromosomes in the GnomAD database, including 108,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (9136 hom., cov: 28)
  • Exomes 𝑓: 0.36 (99337 hom.)
• Consequence: GNAO1 NM_138736.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.93
• Publications: 28 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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 16-56343836-A-G is Benign according to our data. Variant chr16-56343836-A-G is described in ClinVar as Benign. ClinVar VariationId is 585945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138736.3. 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.723+6976A>G		intron	N/A	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.951A>G	p.Lys317Lys	synonymous	Exon 8 of 8	NP_620073.2	P09471-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	ENST00000262494.13	TSL:1	c.951A>G	p.Lys317Lys	synonymous	Exon 8 of 8	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.723+6976A>G		intron	N/A	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000638705.1	TSL:1	c.723+6976A>G		intron	N/A	ENSP00000491223.1	P09471-1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 55766 AN: 119914 Hom.: 9114 Cov.: 28

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.345 AC: 86379 AN: 250710 AF XY: 0.348

Gnomad AFR exome AF: 0.579

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.363 AC: 530211 AN: 1460142 Hom.: 99337 Cov.: 34 AF XY: 0.364 AC XY: 264269 AN XY: 726440

African (AFR) AF: 0.581 AC: 19419 AN: 33436

American (AMR) AF: 0.250 AC: 11183 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 7607 AN: 26100

East Asian (EAS) AF: 0.210 AC: 8313 AN: 39612

South Asian (SAS) AF: 0.454 AC: 39080 AN: 86164

European-Finnish (FIN) AF: 0.271 AC: 14469 AN: 53298

Middle Eastern (MID) AF: 0.298 AC: 1715 AN: 5762

European-Non Finnish (NFE) AF: 0.366 AC: 406570 AN: 1110794

Other (OTH) AF: 0.362 AC: 21855 AN: 60328

GnomAD4 genome AF: 0.465 AC: 55826 AN: 120018 Hom.: 9136 Cov.: 28 AF XY: 0.461 AC XY: 26876 AN XY: 58342

African (AFR) AF: 0.587 AC: 21314 AN: 36326

American (AMR) AF: 0.367 AC: 3966 AN: 10812

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 953 AN: 2488

East Asian (EAS) AF: 0.308 AC: 1045 AN: 3388

South Asian (SAS) AF: 0.508 AC: 2038 AN: 4014

European-Finnish (FIN) AF: 0.332 AC: 2684 AN: 8086

Middle Eastern (MID) AF: 0.404 AC: 84 AN: 208

European-Non Finnish (NFE) AF: 0.434 AC: 22744 AN: 52410

Other (OTH) AF: 0.416 AC: 662 AN: 1590

Alfa AF: 0.364 Hom.: 16571

Bravo AF: 0.406

EpiCase AF: 0.346

EpiControl AF: 0.342

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.64
PhyloP100		2.9
Mutation Taster		=79/21	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: rs1799917; hg19: chr16-56377748; COSMIC: COSV52613707;