chr3-39513403-C-G

Variant names:

• chr3-39513403-C-G
• ENST00000383754.7:c.227C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000383754.7(MOBP):​c.227C>G​(p.Pro76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOBP ENST00000383754.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12735027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOBP	NM_182935.4	c.227C>G	p.Pro76Arg	missense_variant	Exon 4 of 4		NP_891980.1
MOBP	NR_003090.3	n.376C>G		non_coding_transcript_exon_variant	Exon 4 of 6
MOBP	NR_103504.2	n.718C>G		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOBP	ENST00000383754.7	c.227C>G	p.Pro76Arg	missense_variant	Exon 4 of 4	1		ENSP00000373261.3
MOBP	ENST00000424090.5	n.*55C>G		non_coding_transcript_exon_variant	Exon 3 of 5	1		ENSP00000389055.1
MOBP	ENST00000442631.5	n.*20C>G		non_coding_transcript_exon_variant	Exon 3 of 5	1		ENSP00000413771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.227C>G (p.P76R) alteration is located in exon 4 (coding exon 2) of the MOBP gene. This alteration results from a C to G substitution at nucleotide position 227, causing the proline (P) at amino acid position 76 to be replaced by an arginine (R). 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
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.45
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.061
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PROVEAN	Benign	0.88	N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.096	T;T;T;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.53	P;P;P;P
Vest4		0.22
MutPred		0.25		Loss of glycosylation at P76 (P = 0.0058);Loss of glycosylation at P76 (P = 0.0058);Loss of glycosylation at P76 (P = 0.0058);Loss of glycosylation at P76 (P = 0.0058);
MVP		0.043
MPC		0.86
ClinPred		0.20	T
GERP RS		4.2
Mutation Taster		=98/2	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

hg19: chr3-39554894;