Variant 4-102631740-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005908.4(MANBA):c.*317A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 570,402 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 143 hom., cov: 32)

Exomes 𝑓: 0.010 ( 62 hom. )

Consequence

MANBA
NM_005908.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.489

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 4-102631740-T-C is Benign according to our data. Variant chr4-102631740-T-C is described in ClinVar as [Benign]. Clinvar id is 347070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MANBA	NM_005908.4 linkuse as main transcript	c.*317A>G	3_prime_UTR_variant	17/17	ENST00000647097.2
MANBA	XM_047415692.1 linkuse as main transcript	c.*317A>G	3_prime_UTR_variant	18/18
MANBA	XM_047415693.1 linkuse as main transcript	c.*317A>G	3_prime_UTR_variant	18/18
MANBA	XM_047415694.1 linkuse as main transcript	c.*317A>G	3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2 linkuse as main transcript	c.*317A>G		3_prime_UTR_variant	17/17		NM_005908.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4303

AN:

152192

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0792

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.0101

AC:

4202

AN:

418092

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

2013

AN XY:

218194

show subpopulations

Gnomad4 AFR exome

AF:

0.0776

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.00120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000636

Gnomad4 FIN exome

AF:

0.00373

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0284

AC:

4326

AN:

152310

Hom.:

143

Cov.:

AF XY:

0.0272

AC XY:

2023

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0796

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0315

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

- -

Beta-D-mannosidosis

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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