rs899012163

Variant names:

• chr21-33070532-C-A
• rs899012163
• NM_138983.3:c.286C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138983.3(OLIG1):​c.286C>A​(p.Pro96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OLIG1 NM_138983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355
• Publications: 0 publications found

Genes affected

OLIG1 (HGNC:16983): (oligodendrocyte transcription factor 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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 neuron fate commitment. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000227757 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12492859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138983.3. 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
	OLIG1	NM_138983.3	MANE Select	c.286C>A	p.Pro96Thr	missense	Exon 1 of 1	NP_620450.2	Q8TAK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLIG1	ENST00000382348.2	TSL:6 MANE Select	c.286C>A	p.Pro96Thr	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
	ENSG00000227757	ENST00000454622.2	TSL:2	n.201+372G>T		intron	N/A
	ENSG00000227757	ENST00000777421.1		n.91+372G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151932 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1349292 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 665642

African (AFR) AF: 0.00 AC: 0 AN: 27332

American (AMR) AF: 0.00 AC: 0 AN: 30402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23674

East Asian (EAS) AF: 0.00 AC: 0 AN: 30890

South Asian (SAS) AF: 0.00 AC: 0 AN: 75136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063022

Other (OTH) AF: 0.00 AC: 0 AN: 56046

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151932 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74204

African (AFR) AF: 0.0000483 AC: 2 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.060
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	-0.34	N
PhyloP100		0.35
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.22
Sift	Benign	0.48	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.024
MutPred		0.19		Gain of phosphorylation at P96 (P = 0.032)
MVP		0.82
MPC		1.6
ClinPred		0.051	T
GERP RS		1.2
PromoterAI		-0.072	Neutral
Varity_R		0.058
gMVP		0.39
Mutation Taster		=94/6	polymorphism

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: rs899012163; hg19: chr21-34442838;