6-29659361-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206809.4(MOG):c.131T>C(p.Leu44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.709

Genes affected

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.131T>C	p.Leu44Pro	missense_variant	2/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.131T>C	p.Leu44Pro	missense_variant	2/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726672

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

Dec 12, 2023

The c.131T>C (p.L44P) alteration is located in exon 2 (coding exon 2) of the MOG gene. This alteration results from a T to C substitution at nucleotide position 131, causing the leucine (L) at amino acid position 44 to be replaced by a proline (P). 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	0.20
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;.;T;.;.;.;.;.
Eigen	Benign	0.052
Eigen_PC	Benign	0.063
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.68	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.0	L;L;L;.;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.26	T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;D;.;P;D;D;D
Vest4		0.76
MutPred		0.49		Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);Loss of stability (P = 0.0043);
MVP		0.85
MPC		1.0
ClinPred		0.85	D
GERP RS		5.9
Varity_R		0.87
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-29627138;