9-137087006-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016219.5(MAN1B1):c.7G>T(p.Ala3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000295 in 1,594,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MAN1B1
NM_016219.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.18

Publications

0 publications found

Variant links:

Genes affected

MAN1B1 (HGNC:6823): (mannosidase alpha class 1B member 1) This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause autosomal-recessive intellectual disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Dec 2011]

MAN1B1 links:

MAN1B1-DT (HGNC:48715): (MAN1B1 divergent transcript)

MAN1B1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048623055).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN1B1	NM_016219.5	MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 1 of 13	NP_057303.2	Q9UKM7
MAN1B1	NR_045720.2		n.22G>T		non_coding_transcript_exon	Exon 1 of 13
MAN1B1	NR_045721.2		n.22G>T		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN1B1	ENST00000371589.9	TSL:1 MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 1 of 13	ENSP00000360645.4	Q9UKM7
MAN1B1	ENST00000371587.9	TSL:1	n.7G>T		non_coding_transcript_exon	Exon 1 of 14	ENSP00000483132.2	A0A087X064
MAN1B1	ENST00000544448.6	TSL:1	n.7G>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000444966.2	H0YGV7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000945

AC:

AN:

211728

AF XY:

0.0000174

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000291

AC:

AN:

1442430

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

715548

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

41442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25516

East Asian (EAS)

AF:

0.0000513

AC:

AN:

38986

South Asian (SAS)

AF:

0.00

AC:

AN:

82970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50194

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.0000281

AC:

AN:

1104656

Other (OTH)

AF:

0.0000670

AC:

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152390

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74528

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41598

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000334

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Rafiq syndrome (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

5.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.020

REVEL

Benign

0.022

Sift

Benign

0.30

Sift4G

Benign

0.36

Polyphen

0.61

Vest4

0.28

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0215)

MVP

0.17

MPC

0.30

ClinPred

0.28

GERP RS

3.3

PromoterAI

0.0051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.090

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over