Variant 9-137086979-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The ENST00000371587.9(MAN1B1):c.-21C>A variant causes a 5 prime UTR, NMD transcript 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
ENST00000371587.9 5_prime_UTR, NMD_transcript

Scores

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 182 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	Effect	MANE
MAN1B1	NM_016219.5 linkuse as main transcript	upstream_gene_variant	ENST00000371589.9
MAN1B1	XM_006716945.5 linkuse as main transcript	upstream_gene_variant
MAN1B1	NR_045720.2 linkuse as main transcript	upstream_gene_variant
MAN1B1	NR_045721.2 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1B1	ENST00000371589.9 linkuse as main transcript			upstream_gene_variant		1	NM_016219.5	P2

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152276

Hom.:

Cov.:

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

GnomAD3 exomes

AF:

0.000268

AC:

AN:

182732

Hom.:

AF XY:

0.000285

AC XY:

AN XY:

98182

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 SAS exome

AF:

0.0000405

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.:

Cov.:

AF XY:

0.000259

AC XY:

182

AN XY:

702630

show subpopulations

Gnomad4 AFR exome

AF:

0.000516

Gnomad4 AMR exome

AF:

0.000661

Gnomad4 ASJ exome

AF:

0.0000792

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.0000412

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.000730

GnomAD4 genome

AF:

0.000328

AC:

AN:

152394

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74532

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000342

Hom.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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