chr9-137086979-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The ENST00000542372(MAN1B1):​c.-21C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,572,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

MAN1B1
ENST00000542372 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.661
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-DT (HGNC:48715): (MAN1B1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BS1
Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000244 (347/1419744) while in subpopulation MID AF = 0.0043 (23/5346). AF 95% confidence interval is 0.00294. There are 1 homozygotes in GnomAdExome4. There are 182 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAN1B1NM_016219.5 linkc.-21C>A upstream_gene_variant ENST00000371589.9 NP_057303.2 Q9UKM7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAN1B1ENST00000371589.9 linkc.-21C>A upstream_gene_variant 1 NM_016219.5 ENSP00000360645.4 Q9UKM7

Frequencies

GnomAD3 genomes
AF:
0.000328
AC:
50
AN:
152276
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00191
GnomAD2 exomes
AF:
0.000268
AC:
49
AN:
182732
AF XY:
0.000285
show subpopulations
Gnomad AFR exome
AF:
0.000536
Gnomad AMR exome
AF:
0.000595
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000314
Gnomad OTH exome
AF:
0.000417
GnomAD4 exome
AF:
0.000244
AC:
347
AN:
1419744
Hom.:
1
Cov.:
30
AF XY:
0.000259
AC XY:
182
AN XY:
702630
show subpopulations
Gnomad4 AFR exome
AF:
0.000516
AC:
17
AN:
32938
Gnomad4 AMR exome
AF:
0.000661
AC:
25
AN:
37840
Gnomad4 ASJ exome
AF:
0.0000792
AC:
2
AN:
25256
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
38152
Gnomad4 SAS exome
AF:
0.0000370
AC:
3
AN:
81008
Gnomad4 FIN exome
AF:
0.0000412
AC:
2
AN:
48506
Gnomad4 NFE exome
AF:
0.000212
AC:
232
AN:
1091800
Gnomad4 Remaining exome
AF:
0.000730
AC:
43
AN:
58898
Heterozygous variant carriers
0
19
38
58
77
96
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.000328
AC:
50
AN:
152394
Hom.:
0
Cov.:
34
AF XY:
0.000349
AC XY:
26
AN XY:
74532
show subpopulations
Gnomad4 AFR
AF:
0.000481
AC:
0.000480839
AN:
0.000480839
Gnomad4 AMR
AF:
0.000588
AC:
0.000587851
AN:
0.000587851
Gnomad4 ASJ
AF:
0.000288
AC:
0.000288184
AN:
0.000288184
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000220
AC:
0.000220439
AN:
0.000220439
Gnomad4 OTH
AF:
0.00189
AC:
0.00189036
AN:
0.00189036
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000342
Hom.:
0
Bravo
AF:
0.000366

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Intellectual Disability, Recessive Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
14
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=300/0
polymorphism

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.

Other links and lift over

dbSNP: rs367593587; hg19: chr9-139981431; API