NM_175747.2:c.688G>C

Variant names:

• chr6-137493483-C-G
• NM_175747.2:c.688G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175747.2(OLIG3):​c.688G>C​(p.Gly230Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,421,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OLIG3 NM_175747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.648
• Publications: 0 publications found

Genes affected

OLIG3 (HGNC:18003): (oligodendrocyte transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in neuron differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II; spinal cord motor neuron cell fate specification; and spinal cord motor neuron migration. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000306409 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175747.2. 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
	OLIG3	NM_175747.2	MANE Select	c.688G>C	p.Gly230Arg	missense	Exon 1 of 1	NP_786923.1	Q7RTU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLIG3	ENST00000367734.4	TSL:6 MANE Select	c.688G>C	p.Gly230Arg	missense	Exon 1 of 1	ENSP00000356708.2	Q7RTU3
	ENSG00000306409	ENST00000818123.1		n.191+4632G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1421564 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 704224

African (AFR) AF: 0.00 AC: 0 AN: 32840

American (AMR) AF: 0.00 AC: 0 AN: 39742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25000

East Asian (EAS) AF: 0.00 AC: 0 AN: 38428

South Asian (SAS) AF: 0.00 AC: 0 AN: 81520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1096470

Other (OTH) AF: 0.00 AC: 0 AN: 58898

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.83	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.7	L
PhyloP100		0.65
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.65
MutPred		0.28		Loss of glycosylation at S229 (P = 0.0379)
MVP		0.58
MPC		1.7
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.41
gMVP		0.67
Mutation Taster		=48/52	disease causing

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

hg19: chr6-137814620;