rs1596787365

Variant names:

• chr16-56192271-C-T
• rs1596787365
• NM_020988.3:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_020988.3(GNAO1):​c.36C>T​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNAO1 NM_020988.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 16-56192271-C-T is Benign according to our data. Variant chr16-56192271-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 794714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.

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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 9	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.36C>T	p.Ala12Ala	synonymous	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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 9	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000262494.13	TSL:1	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 8	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000638705.1	TSL:1	c.36C>T	p.Ala12Ala	synonymous	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 benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		1.3
PromoterAI		-0.038	Neutral

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: rs1596787365; hg19: chr16-56226183;