3-39502578-C-T

Variant names:

• chr3-39502578-C-T
• rs755066817
• NM_001393704.1:c.250C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393704.1(MOBP):​c.250C>T​(p.Pro84Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000412 in 1,575,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: MOBP NM_001393704.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• Publications: 2 publications found

Genes affected

MOBP (HGNC:7189): (myelin associated oligodendrocyte basic protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be a structural constituent of myelin sheath. Predicted to be involved in nervous system development. Predicted to be located in mitochondrion. Predicted to be active in cortical actin cytoskeleton. Implicated in frontotemporal dementia. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285885 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07840517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOBP	NM_001393704.1	c.250C>T	p.Pro84Ser	missense_variant	Exon 4 of 4	ENST00000684792.1	NP_001380633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOBP	ENST00000684792.1	c.250C>T	p.Pro84Ser	missense_variant	Exon 4 of 4		NM_001393704.1	ENSP00000508923.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.0000376 AC: 7 AN: 186196 AF XY: 0.0000389

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000239

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.0000344 AC: 49 AN: 1423684 Hom.: 0 Cov.: 32 AF XY: 0.0000326 AC XY: 23 AN XY: 706524

African (AFR) AF: 0.00 AC: 0 AN: 32896

American (AMR) AF: 0.000220 AC: 9 AN: 40950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 38306

South Asian (SAS) AF: 0.00 AC: 0 AN: 82568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35926

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5714

European-Non Finnish (NFE) AF: 0.0000245 AC: 27 AN: 1102150

Other (OTH) AF: 0.000185 AC: 11 AN: 59442

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74366

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.000458 AC: 7 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68046

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000170

ExAC AF: 0.0000264 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

MOBP-related disorder Uncertain:1

Dec 22, 2022

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The MOBP c.322C>T variant is predicted to result in the amino acid substitution p.Pro108Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-39544069-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.65	.;.;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;.
PhyloP100		3.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.010	N;N;N
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D;D;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.94	P;P;.
Vest4		0.30
MutPred		0.27		Gain of phosphorylation at P84 (P = 0.0143);Gain of phosphorylation at P84 (P = 0.0143);.;
MVP		0.043
ClinPred		0.29	T
GERP RS		3.5
Varity_R		0.18
gMVP		0.10
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs755066817; hg19: chr3-39544069;