21-33070869-T-A

Variant names:

• chr21-33070869-T-A
• rs899106642
• NM_138983.3:c.623T>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.623T>A​(p.Val208Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000089 in 1,124,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V208A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: OLIG1 NM_138983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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=0.24563089).

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.623T>A	p.Val208Glu	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.623T>A	p.Val208Glu	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
	ENSG00000227757	ENST00000454622.2	TSL:2	n.201+35A>T		intron	N/A
	ENSG00000227757	ENST00000777421.1		n.91+35A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.90e-7 AC: 1 AN: 1124094 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 540012

African (AFR) AF: 0.00 AC: 0 AN: 22506

American (AMR) AF: 0.00 AC: 0 AN: 8140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14478

East Asian (EAS) AF: 0.00 AC: 0 AN: 25278

South Asian (SAS) AF: 0.00 AC: 0 AN: 37296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2984

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 943614

Other (OTH) AF: 0.00 AC: 0 AN: 44778

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	0.34	N
PhyloP100		0.074
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.38	T
Polyphen		0.072	B
Vest4		0.36
MutPred		0.34		Gain of solvent accessibility (P = 9e-04)
MVP		0.77
MPC		2.2
ClinPred		0.21	T
GERP RS		2.3
PromoterAI		0.050	Neutral
Varity_R		0.30
gMVP		0.36
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: rs899106642; hg19: chr21-34443175;