6-137493654-G-A

Position:

• chr6-137493654-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_175747.2(OLIG3):​c.517C>T​(p.His173Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OLIG3 NM_175747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

Genes affected

OLIG3 (HGNC:18003): (oligodendrocyte transcription factor 3) Enables sequence-specific double-stranded 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 negative regulation of transcription by RNA polymerase II; spinal cord motor neuron cell fate specification; and spinal cord motor neuron migration. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25775534).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG3	NM_175747.2	c.517C>T	p.His173Tyr	missense_variant	1/1	ENST00000367734.4	NP_786923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG3	ENST00000367734.4	c.517C>T	p.His173Tyr	missense_variant	1/1	6	NM_175747.2	ENSP00000356708.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1456638 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 724822

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 13, 2023

The c.517C>T (p.H173Y) alteration is located in exon 1 (coding exon 1) of the OLIG3 gene. This alteration results from a C to T substitution at nucleotide position 517, causing the histidine (H) at amino acid position 173 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	1.0	T
Polyphen		0.92	P
Vest4		0.41
MutPred		0.30		Gain of phosphorylation at H173 (P = 0.0351);
MVP		0.22
MPC		1.0
ClinPred		0.63	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.54

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: chr6-137814791;