Variant 4-6587125-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015274.3(MAN2B2):c.521C>T(p.Ser174Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MAN2B2
NM_015274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56

Variant links:

Genes affected

MAN2B2 (HGNC:29623): (mannosidase alpha class 2B member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN2B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2B2	NM_015274.3 linkuse as main transcript	c.521C>T	p.Ser174Phe	missense_variant	4/19	ENST00000285599.8
MAN2B2	NM_001292038.2 linkuse as main transcript	c.521C>T	p.Ser174Phe	missense_variant	4/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2B2	ENST00000285599.8 linkuse as main transcript	c.521C>T	p.Ser174Phe	missense_variant	4/19	1	NM_015274.3	P1	Q9Y2E5-1
MAN2B2	ENST00000504248.5 linkuse as main transcript	c.521C>T	p.Ser174Phe	missense_variant	4/19	2
MAN2B2	ENST00000505907.1 linkuse as main transcript	c.518C>T	p.Ser173Phe	missense_variant	4/17	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

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:

0.0000319

AC:

AN:

250654

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461478

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000164

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000379

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.521C>T (p.S174F) alteration is located in exon 4 (coding exon 4) of the MAN2B2 gene. This alteration results from a C to T substitution at nucleotide position 521, causing the serine (S) at amino acid position 174 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.98

D;D

Vest4

0.90

MVP

0.40

MPC

0.60

ClinPred

0.83

GERP RS

4.1

Varity_R

0.88

gMVP

0.85

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

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