Variant rs561720564 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000528.4(MAN2B1):c.2101G>T(p.Val701Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

MAN2B1
NM_000528.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Variant links:

Genes affected

MAN2B1 (HGNC:6826): (mannosidase alpha class 2B member 1) This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

MAN2B1 links:

MAN2B1 (HGNC:):

MAN2B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2B1	NM_000528.4 linkuse as main transcript	c.2101G>T	p.Val701Phe	missense_variant	17/24	ENST00000456935.7	NP_000519.2	O00754-1
MAN2B1	NM_001173498.2 linkuse as main transcript	c.2098G>T	p.Val700Phe	missense_variant	17/24		NP_001166969.1	O00754-2A8K6A7
MAN2B1	XM_005259913.3 linkuse as main transcript	c.2104G>T	p.Val702Phe	missense_variant	17/24		XP_005259970.1
MAN2B1	XM_047438841.1 linkuse as main transcript	c.1000G>T	p.Val334Phe	missense_variant	10/17		XP_047294797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAN2B1	ENST00000456935.7 linkuse as main transcript	c.2101G>T	p.Val701Phe	missense_variant	17/24	1	NM_000528.4	ENSP00000395473.2	O00754-1
MAN2B1	ENST00000221363.8 linkuse as main transcript	c.2098G>T	p.Val700Phe	missense_variant	17/24	1		ENSP00000221363.4	O00754-2
MAN2B1	ENST00000466794.5 linkuse as main transcript	n.2691G>T		non_coding_transcript_exon_variant	15/22	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251428

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;.

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

-0.027

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.046

D;D

Polyphen

1.0

D;.

Vest4

0.74

MutPred

0.79

Gain of sheet (P = 0.0827);.;

MVP

0.76

MPC

0.85

ClinPred

0.92

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.54

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over