rs2272697

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005908.4(MANBA):c.2368T>C(p.Leu790Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,613,786 control chromosomes in the GnomAD database, including 224,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23406 hom., cov: 32)

Exomes 𝑓: 0.52 ( 201098 hom. )

Consequence

MANBA
NM_005908.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.00

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 links:

MANBA (HGNC:):

MANBA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 4-102634835-A-G is Benign according to our data. Variant chr4-102634835-A-G is described in ClinVar as [Benign]. Clinvar id is 95320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-102634835-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANBA	NM_005908.4 linkuse as main transcript	c.2368T>C	p.Leu790Leu	synonymous_variant	16/17	ENST00000647097.2	NP_005899.3	O00462
MANBA	XM_047415692.1 linkuse as main transcript	c.2293T>C	p.Leu765Leu	synonymous_variant	17/18		XP_047271648.1
MANBA	XM_047415693.1 linkuse as main transcript	c.2293T>C	p.Leu765Leu	synonymous_variant	17/18		XP_047271649.1
MANBA	XM_047415694.1 linkuse as main transcript	c.1720T>C	p.Leu574Leu	synonymous_variant	12/13		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2 linkuse as main transcript	c.2368T>C	p.Leu790Leu	synonymous_variant	16/17		NM_005908.4	ENSP00000495247.1		O00462

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83484

AN:

151954

Hom.:

23368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.541

AC:

135905

AN:

251324

Hom.:

37947

AF XY:

0.529

AC XY:

71883

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.529

Gnomad SAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.521

AC:

762192

AN:

1461714

Hom.:

201098

Cov.:

AF XY:

0.518

AC XY:

376758

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.634

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.493

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.518

Gnomad4 OTH exome

AF:

0.532

GnomAD4 genome

AF:

0.550

AC:

83569

AN:

152072

Hom.:

23406

Cov.:

AF XY:

0.548

AC XY:

40779

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.618

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.549

Alfa

AF:

0.522

Hom.:

26597

Bravo

AF:

0.567

Asia WGS

AF:

0.505

AC:

1753

AN:

3478

EpiCase

AF:

0.516

EpiControl

AF:

0.504

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 21, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 16, 2013	- -

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Beta-D-mannosidosis

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.6

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over