21-33070794-C-T

Variant names:

• chr21-33070794-C-T
• rs2123303594
• NM_138983.3:c.548C>T

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.548C>T​(p.Ala183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000674 in 148,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (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: 1.03
• 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=0.2509398).

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.548C>T	p.Ala183Val	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.548C>T	p.Ala183Val	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
	ENSG00000227757	ENST00000454622.2	TSL:2	n.201+110G>A		intron	N/A
	ENSG00000227757	ENST00000777421.1		n.91+110G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148274 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1050920 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 496458

African (AFR) AF: 0.00 AC: 0 AN: 21644

American (AMR) AF: 0.00 AC: 0 AN: 7306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12846

East Asian (EAS) AF: 0.00 AC: 0 AN: 23872

South Asian (SAS) AF: 0.00 AC: 0 AN: 19632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 901470

Other (OTH) AF: 0.00 AC: 0 AN: 41284

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148380 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72362

African (AFR) AF: 0.00 AC: 0 AN: 41146

American (AMR) AF: 0.00 AC: 0 AN: 14936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66658

Other (OTH) AF: 0.00 AC: 0 AN: 2060

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	0.14
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.29
Sift	Benign	0.090	T
Sift4G	Benign	0.068	T
Polyphen		0.034	B
Vest4		0.18
MutPred		0.31		Loss of helix (P = 0.0167)
MVP		0.81
MPC		1.7
ClinPred		0.16	T
GERP RS		2.5
PromoterAI		-0.023	Neutral
Varity_R		0.069
gMVP		0.52
Mutation Taster		=93/7	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: rs2123303594; hg19: chr21-34443100;