rs1065375

Variant names:

• chr16-56334777-C-A
• rs1065375
• NM_020988.3:c.513C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56334777-C-A
• chr16-56334777-C-G
• chr16-56334777-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_020988.3(GNAO1):​c.513C>A​(p.Thr171Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T171T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GNAO1 NM_020988.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 21 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)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=-0.914 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.513C>A	p.Thr171Thr	synonymous_variant	Exon 5 of 9	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.513C>A	p.Thr171Thr	synonymous_variant	Exon 5 of 8		NP_620073.2
GNAO1	XM_011523003.4	c.387C>A	p.Thr129Thr	synonymous_variant	Exon 5 of 9		XP_011521305.1
GNAO1	XR_007064866.1	n.1260C>A		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.513C>A	p.Thr171Thr	synonymous_variant	Exon 5 of 9	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	1.8
DANN	Benign	0.84
PhyloP100		-0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1065375; hg19: chr16-56368689;