3-39502508-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001393704.1(MOBP):c.207-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,560,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (0 hom.)
• Consequence: MOBP NM_001393704.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.91

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-39502508-G-A is Benign according to our data. Variant chr3-39502508-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3057625.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOBP	NM_001393704.1	c.207-27G>A		intron_variant		ENST00000684792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOBP	ENST00000684792.1	c.207-27G>A		intron_variant			NM_001393704.1
	ENST00000648447.1	n.60C>T		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 118 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000835 AC: 141 AN: 168908 Hom.: 0 AF XY: 0.000894 AC XY: 83 AN XY: 92892

Gnomad AFR exome AF: 0.000115

Gnomad AMR exome AF: 0.000216

Gnomad ASJ exome AF: 0.00401

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000248

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000422

GnomAD4 exome AF: 0.000853 AC: 1201 AN: 1408410 Hom.: 0 Cov.: 32 AF XY: 0.000854 AC XY: 596 AN XY: 697508

Gnomad4 AFR exome AF: 0.0000926

Gnomad4 AMR exome AF: 0.000257

Gnomad4 ASJ exome AF: 0.00342

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000653

Gnomad4 NFE exome AF: 0.000946

Gnomad4 OTH exome AF: 0.000746

GnomAD4 genome AF: 0.000775 AC: 118 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49 AN XY: 74496

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.000744

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MOBP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 08, 2021

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
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 27

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

Publications

LitVar

Other links and lift over

dbSNP: rs185064368; hg19: chr3-39543999;