chr9-137087027-G-A

Variant names:

• chr9-137087027-G-A
• NM_016219.5:c.28G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016219.5(MAN1B1):​c.28G>A​(p.Gly10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,486 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.

• 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: -0.723

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057740122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1B1	NM_016219.5	c.28G>A	p.Gly10Arg	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.28G>A	p.Gly10Arg	missense_variant	Exon 1 of 13	1	NM_016219.5	ENSP00000360645.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449486 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719960

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: 0.00000181

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	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.010
Sift	Benign	0.29	T
Sift4G	Benign	0.61	T
Polyphen		0.021	B
Vest4		0.16
MutPred		0.27		Gain of MoRF binding (P = 0.0081);
MVP		0.17
MPC		0.090
ClinPred		0.071	T
GERP RS		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.041
gMVP		0.067

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: chr9-139981479; COSMIC: COSV64306547; COSMIC: COSV64306547;