Variant chr4-102631701-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005908.4(MANBA):c.*356G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 531,228 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 150 hom., cov: 32)

Exomes 𝑓: 0.042 ( 341 hom. )

Consequence

MANBA
NM_005908.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.517

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=-0.84).

BP6

Variant 4-102631701-C-T is Benign according to our data. Variant chr4-102631701-C-T is described in ClinVar as [Benign]. Clinvar id is 347069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-102631701-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0431 (6561/152238) while in subpopulation EAS AF= 0.0548 (284/5180). AF 95% confidence interval is 0.0496. There are 150 homozygotes in gnomad4. There are 3220 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 150 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
MANBA	NM_005908.4 linkuse as main transcript	c.*356G>A	3_prime_UTR_variant	17/17	ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1 linkuse as main transcript	c.*356G>A	3_prime_UTR_variant	18/18		XP_047271648.1
MANBA	XM_047415693.1 linkuse as main transcript	c.*356G>A	3_prime_UTR_variant	18/18		XP_047271649.1
MANBA	XM_047415694.1 linkuse as main transcript	c.*356G>A	3_prime_UTR_variant	13/13		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2 linkuse as main transcript	c.*356G>A		3_prime_UTR_variant	17/17		NM_005908.4	ENSP00000495247	P1

Frequencies

GnomAD3 genomes

AF:

0.0431

AC:

6554

AN:

152120

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0551

Gnomad SAS

AF:

0.0409

Gnomad FIN

AF:

0.0622

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0383

GnomAD4 exome

AF:

0.0421

AC:

15950

AN:

378990

Hom.:

341

Cov.:

AF XY:

0.0413

AC XY:

8082

AN XY:

195604

show subpopulations

Gnomad4 AFR exome

AF:

0.0332

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.0470

Gnomad4 SAS exome

AF:

0.0321

Gnomad4 FIN exome

AF:

0.0557

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0424

GnomAD4 genome

AF:

0.0431

AC:

6561

AN:

152238

Hom.:

150

Cov.:

AF XY:

0.0433

AC XY:

3220

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.0548

Gnomad4 SAS

AF:

0.0415

Gnomad4 FIN

AF:

0.0622

Gnomad4 NFE

AF:

0.0457

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0389

Hom.:

136

Bravo

AF:

0.0410

Asia WGS

AF:

0.0480

AC:

168

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.84

CADD

Benign

6.0

DANN

Benign

0.75

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