dbSNP rs1559424420: MOBP:p.Ser129_Arg138del (chr3-39502614-AAGCCACGGTCCCCTCCGAGGTCTGAGCGTC-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM4BP6

The NM_001393704.1(MOBP):c.384_413delGTCCCCTCCGAGGTCTGAGCGTCAGCCACG(p.Ser129_Arg138del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 151,346 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000095 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MOBP
NM_001393704.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.71

Publications

0 publications found

Variant links:

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]

MOBP links:

ENSG00000285885 (HGNC:):

ENSG00000285885 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001393704.1.

BP6

Variant 3-39502614-AAGCCACGGTCCCCTCCGAGGTCTGAGCGTC-A is Benign according to our data. Variant chr3-39502614-AAGCCACGGTCCCCTCCGAGGTCTGAGCGTC-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052120.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOBP	NM_001393704.1 link	c.384_413delGTCCCCTCCGAGGTCTGAGCGTCAGCCACG	p.Ser129_Arg138del	disruptive_inframe_deletion	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 link	c.384_413delGTCCCCTCCGAGGTCTGAGCGTCAGCCACG	p.Ser129_Arg138del	disruptive_inframe_deletion	Exon 4 of 4		NM_001393704.1	ENSP00000508923.1		Q13875-1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000590

AC:

AN:

169576

AF XY:

0.0000107

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000761

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000951

AC:

134

AN:

1409402

Hom.:

AF XY:

0.000102

AC XY:

AN XY:

698118

show subpopulations

African (AFR)

AF:

0.000123

AC:

AN:

32512

American (AMR)

AF:

0.0000516

AC:

AN:

38788

Ashkenazi Jewish (ASJ)

AF:

0.0000784

AC:

AN:

25514

East Asian (EAS)

AF:

0.000134

AC:

AN:

37410

South Asian (SAS)

AF:

0.0000247

AC:

AN:

81030

European-Finnish (FIN)

AF:

0.0000570

AC:

AN:

35078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0000987

AC:

108

AN:

1094442

Other (OTH)

AF:

0.000153

AC:

AN:

58946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151346

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73866

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41160

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67762

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MOBP-related disorder

Benign:1

Jul 19, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Mutation Taster

=129/71

disease causing (fs/PTC)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1559424420

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over