chr9-137087006-G-A

Variant names:

• chr9-137087006-G-A
• rs573766677
• NM_016219.5:c.7G>A

Variant summary

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

The NM_016219.5(MAN1B1):​c.7G>A​(p.Ala3Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,442,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAN1B1 NM_016219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18

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)

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=0.116842896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1B1	NM_016219.5	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 13	ENST00000371589.9	NP_057303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 13	1	NM_016219.5	ENSP00000360645.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000945 AC: 2 AN: 211728 Hom.: 0 AF XY: 0.00000872 AC XY: 1 AN XY: 114620

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000373

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442430 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715548

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000241

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.021
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.041	D
Polyphen		0.61	P
Vest4		0.31
MutPred		0.28		Gain of glycosylation at A3 (P = 0.0123);
MVP		0.19
MPC		0.34
ClinPred		0.77	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.13

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

Other links and lift over

dbSNP: rs573766677; hg19: chr9-139981458;