17-31295605-T-C

Position:

• chr17-31295605-T-C

Variant summary

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

The NM_002544.5(OMG):​c.727A>G​(p.Met243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OMG NM_002544.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723

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]

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]

OMG (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=0.09263325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OMG	NM_002544.5	c.727A>G	p.Met243Val	missense_variant	2/2	ENST00000247271.5	NP_002535.3
NF1	NM_001042492.3	c.4836-30215T>C		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-30215T>C		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OMG	ENST00000247271.5	c.727A>G	p.Met243Val	missense_variant	2/2	1	NM_002544.5	ENSP00000247271.4
NF1	ENST00000358273.9	c.4836-30215T>C		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727228

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: 8.99e-7

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

Aug 01, 2024

The c.727A>G (p.M243V) alteration is located in exon 2 (coding exon 1) of the OMG gene. This alteration results from a A to G substitution at nucleotide position 727, causing the methionine (M) at amino acid position 243 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	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.051
Sift	Benign	0.19	T
Sift4G	Benign	0.69	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.42		Gain of catalytic residue at M243 (P = 0.0555);
MVP		0.36
MPC		0.39
ClinPred		0.037	T
GERP RS		3.2
Varity_R		0.086
gMVP		0.29

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: chr17-29622623;