Variant 21-33070794-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

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]

OLIG1 links:

ENSG00000227757 (HGNC:):

ENSG00000227757 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2509398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG1	NM_138983.3 linkuse as main transcript	c.548C>T	p.Ala183Val	missense_variant	1/1	ENST00000382348.2	NP_620450.2	Q8TAK6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG1	ENST00000382348.2 linkuse as main transcript	c.548C>T	p.Ala183Val	missense_variant	1/1	6	NM_138983.3	ENSP00000371785.1		Q8TAK6
ENSG00000227757	ENST00000454622.2 linkuse as main transcript	n.201+110G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000674

AC:

AN:

148274

Hom.:

Cov.:

show subpopulations

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:

AN:

1050920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

496458

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000674

AC:

AN:

148380

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.548C>T (p.A183V) alteration is located in exon 1 (coding exon 1) of the OLIG1 gene. This alteration results from a C to T substitution at nucleotide position 548, causing the alanine (A) at amino acid position 183 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.026

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.82

REVEL

Benign

0.29

Sift

Benign

0.090

Sift4G

Benign

0.068

Polyphen

0.034

Vest4

0.18

MutPred

0.31

Loss of helix (P = 0.0167);

MVP

0.81

MPC

1.7

ClinPred

0.16

GERP RS

2.5

Varity_R

0.069

gMVP

0.52

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over