17-31295094-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002544.5(OMG):c.1238C>T(p.Thr413Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

OMG
NM_002544.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65

Variant links:

Genes affected

OMG (HGNC:8135): (oligodendrocyte myelin glycoprotein) Predicted to enable identical protein binding activity. Predicted to be involved in neuron projection regeneration. Predicted to act upstream of or within regulation of collateral sprouting of intact axon in response to injury. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OMG links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05612716).

BS2

High AC in GnomAdExome at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OMG	NM_002544.5 linkuse as main transcript	c.1238C>T	p.Thr413Ile	missense_variant	2/2	ENST00000247271.5
NF1	NM_001042492.3 linkuse as main transcript	c.4835+29755G>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.4772+29755G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMG	ENST00000247271.5 linkuse as main transcript	c.1238C>T	p.Thr413Ile	missense_variant	2/2	1	NM_002544.5	P1
NF1	ENST00000358273.9 linkuse as main transcript	c.4835+29755G>A		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

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:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251352

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727206

show subpopulations

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:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74484

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:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Aug 04, 2023

The c.1238C>T (p.T413I) alteration is located in exon 2 (coding exon 1) of the OMG gene. This alteration results from a C to T substitution at nucleotide position 1238, causing the threonine (T) at amino acid position 413 to be replaced by an isoleucine (I). 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

0.089

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

0.031

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.66

M_CAP

Benign

0.011

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.25

REVEL

Benign

0.055

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

0.077

Vest4

0.31

MutPred

0.32

Loss of disorder (P = 0.0206);

MVP

0.42

MPC

0.42

ClinPred

0.18

GERP RS

5.0

Varity_R

0.14

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over