chr3-39502259-G-T

Variant names:

• chr3-39502259-G-T
• rs777895010
• NM_001393704.1:c.190G>T

Variant summary

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

The NM_001393704.1(MOBP):​c.190G>T​(p.Ala64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A64T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MOBP NM_001393704.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• 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]

ENSG00000285885 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOBP	NM_001393704.1	c.190G>T	p.Ala64Ser	missense_variant	Exon 3 of 4	ENST00000684792.1	NP_001380633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOBP	ENST00000684792.1	c.190G>T	p.Ala64Ser	missense_variant	Exon 3 of 4		NM_001393704.1	ENSP00000508923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461586 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727102

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;.;.;.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	.;.;.;.;.;.;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L;L
PhyloP100		6.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.097	T;D;T;T;T;D;D
Sift4G	Uncertain	0.060	T;T;T;T;T;T;T
Polyphen		0.73	P;P;P;P;P;P;.
Vest4		0.30
MutPred		0.52		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.47
MPC		1.7
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.19
gMVP		0.36
Mutation Taster		=85/15	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: rs777895010; hg19: chr3-39543750;