rs797045687

Positions:

• chr9-137107649-G-A
• chr9-137107649-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000371589.9(MAN1B1):​c.1883G>A​(p.Ser628Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S628I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAN1B1 ENST00000371589.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08789259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1B1	NM_016219.5	c.1883G>A	p.Ser628Asn	missense_variant	12/13	ENST00000371589.9	NP_057303.2
MAN1B1	XM_006716945.5	c.1883G>A	p.Ser628Asn	missense_variant	12/12		XP_006717008.1
MAN1B1	NR_045720.2	n.1873G>A		non_coding_transcript_exon_variant	12/13
MAN1B1	NR_045721.2	n.2029G>A		non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9	c.1883G>A	p.Ser628Asn	missense_variant	12/13	1	NM_016219.5	ENSP00000360645	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457378 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 725284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.7
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.64	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	2.5	N;.
REVEL	Benign	0.16
Sift	Benign	0.64	T;.
Sift4G	Benign	0.54	T;T
Polyphen		0.0	B;.
Vest4		0.26
MutPred		0.50		Loss of disorder (P = 0.085);.;
MVP		0.49
MPC		0.070
ClinPred		0.058	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140002101;