NM_020988.3:c.38T>C

Variant names:

• chr16-56192273-T-C
• rs1555499768
• NM_020988.3:c.38T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_020988.3(GNAO1):​c.38T>C​(p.Leu13Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNAO1 NM_020988.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.83
• Publications: 1 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-DT (HGNC:27543): (GNAO1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-56192273-T-C is Pathogenic according to our data. Variant chr16-56192273-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 493183.Status of the report is criteria_provided_single_submitter, 1 stars.

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.38T>C	p.Leu13Pro	missense	Exon 1 of 9	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.38T>C	p.Leu13Pro	missense	Exon 1 of 8	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.38T>C	p.Leu13Pro	missense	Exon 1 of 9	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000262494.13	TSL:1	c.38T>C	p.Leu13Pro	missense	Exon 1 of 8	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000638705.1	TSL:1	c.38T>C	p.Leu13Pro	missense	Exon 1 of 8	ENSP00000491223.1	P09471-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.39
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.0070	B
Vest4		0.34
MutPred		0.48		Gain of glycosylation at L13 (P = 0.0162)
MVP		0.87
MPC		2.1
ClinPred		0.81	D
GERP RS		3.6
PromoterAI		0.012	Neutral
Varity_R		0.95
gMVP		1.0

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: rs1555499768; hg19: chr16-56226185;