21-33070970-C-G

Position:

• chr21-33070970-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138983.3(OLIG1):​c.724C>G​(p.Pro242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OLIG1 NM_138983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.956

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]

(HGNC:):

ACMG classification

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=0.25074482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLIG1	NM_138983.3	c.724C>G	p.Pro242Ala	missense_variant	1/1	ENST00000382348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLIG1	ENST00000382348.2	c.724C>G	p.Pro242Ala	missense_variant	1/1		NM_138983.3	P1
	ENST00000454622.2	n.135G>C		non_coding_transcript_exon_variant	1/2	2
OLIG1	ENST00000426947.5	c.7C>G	p.Pro3Ala	missense_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.724C>G (p.P242A) alteration is located in exon 1 (coding exon 1) of the OLIG1 gene. This alteration results from a C to G substitution at nucleotide position 724, causing the proline (P) at amino acid position 242 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	-0.20	N
MutationTaster	Benign	0.95	N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.32
Sift	Benign	0.20	T
Sift4G	Benign	0.39	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.44		Gain of catalytic residue at P242 (P = 0.0042);
MVP		0.62
MPC		1.4
ClinPred		0.22	T
GERP RS		2.9
Varity_R		0.035
gMVP		0.36

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.

Other links and lift over

hg19: chr21-34443276;