Genetic Variant MANBA:c.2416-10dupT (chr4-102632290-G-GA) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005908.4(MANBA):c.2416-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0038 ( 0 hom. )

Consequence

MANBA
NM_005908.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.178

Publications

3 publications found

Variant links:

Genes affected

MANBA (HGNC:6831): (mannosidase beta) This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]

MANBA Gene-Disease associations (from GenCC):

beta-mannosidosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

MANBA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 4-102632290-G-GA is Benign according to our data. Variant chr4-102632290-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1169163.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005908.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	NM_005908.4	MANE Select	c.2416-10dupT		intron	N/A	NP_005899.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MANBA	ENST00000647097.2	MANE Select	c.2416-10_2416-9insT	intron	N/A	ENSP00000495247.1	O00462
MANBA	ENST00000642252.1		c.2554-10_2554-9insT	intron	N/A	ENSP00000495483.1	A0A2R8YEC9
MANBA	ENST00000954426.1		c.2515-10_2515-9insT	intron	N/A	ENSP00000624485.1

Frequencies

GnomAD3 genomes

AF:

0.000169

AC:

AN:

148342

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000333

Gnomad ASJ

AF:

0.000585

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000856

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.000492

GnomAD2 exomes

AF:

0.00147

AC:

301

AN:

205224

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.000585

Gnomad AMR exome

AF:

0.000590

Gnomad ASJ exome

AF:

0.00146

Gnomad EAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.000401

GnomAD4 exome

AF:

0.00381

AC:

4660

AN:

1223020

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2259

AN XY:

613372

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00188

AC:

AN:

28224

American (AMR)

AF:

0.000388

AC:

AN:

41276

Ashkenazi Jewish (ASJ)

AF:

0.00290

AC:

AN:

22770

East Asian (EAS)

AF:

0.00164

AC:

AN:

34836

South Asian (SAS)

AF:

0.00320

AC:

243

AN:

75936

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

47292

Middle Eastern (MID)

AF:

0.00448

AC:

AN:

5138

European-Non Finnish (NFE)

AF:

0.00436

AC:

3996

AN:

916342

Other (OTH)

AF:

0.00307

AC:

157

AN:

51206

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

601

1203

1804

2406

3007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000168

AC:

AN:

148448

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

AN XY:

72284

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40724

American (AMR)

AF:

0.000333

AC:

AN:

15020

Ashkenazi Jewish (ASJ)

AF:

0.000585

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.000857

AC:

AN:

4666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000180

AC:

AN:

66626

Other (OTH)

AF:

0.000488

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00795

Hom.:

1436

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Beta-D-mannosidosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-102632290-GAA-GAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over