3-39502842-C-T

Variant names:

• chr3-39502842-C-T
• rs1188260744
• NM_001393704.1:c.514C>T

Variant summary

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

The NM_001393704.1(MOBP):​c.514C>T​(p.Arg172Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,333,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R172S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: MOBP NM_001393704.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2517402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOBP	NM_001393704.1	c.514C>T	p.Arg172Cys	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.514C>T	p.Arg172Cys	missense_variant	Exon 4 of 4		NM_001393704.1	ENSP00000508923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000225 AC: 30 AN: 1333042 Hom.: 0 Cov.: 26 AF XY: 0.0000258 AC XY: 17 AN XY: 658314

African (AFR) AF: 0.00 AC: 0 AN: 30248

American (AMR) AF: 0.0000309 AC: 1 AN: 32366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23448

East Asian (EAS) AF: 0.00 AC: 0 AN: 35496

South Asian (SAS) AF: 0.00 AC: 0 AN: 75768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33288

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5514

European-Non Finnish (NFE) AF: 0.0000259 AC: 27 AN: 1040902

Other (OTH) AF: 0.0000179 AC: 1 AN: 56012

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	.;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.81	L;L;.
PhyloP100		1.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.45
MutPred		0.38		Loss of methylation at R172 (P = 0.0018);Loss of methylation at R172 (P = 0.0018);.;
MVP		0.14
ClinPred		0.80	D
GERP RS		3.5
Varity_R		0.19
gMVP		0.14
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1188260744; hg19: chr3-39544333; COSMIC: COSV60655314; COSMIC: COSV60655314;