ENST00000371587.9:n.-21C>G

Variant names:

• chr9-137086915-A-G
• rs1830375545
• ENST00000683135.1:n.-85A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000371587.9(MAN1B1):​n.-85A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000009 in 1,110,784 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: 0.0000090 (0 hom.)
• Consequence: MAN1B1 ENST00000371587.9 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1B1	NM_016219.5	c.-85A>G		upstream_gene_variant		ENST00000371589.9	NP_057303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9	c.-85A>G		upstream_gene_variant		1	NM_016219.5	ENSP00000360645.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000900 AC: 10 AN: 1110784 Hom.: 0 Cov.: 16 AF XY: 0.00000894 AC XY: 5 AN XY: 559554

African (AFR) AF: 0.00 AC: 0 AN: 26252

American (AMR) AF: 0.00 AC: 0 AN: 35276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23368

East Asian (EAS) AF: 0.00 AC: 0 AN: 34474

South Asian (SAS) AF: 0.00 AC: 0 AN: 73374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3876

European-Non Finnish (NFE) AF: 0.0000121 AC: 10 AN: 826906

Other (OTH) AF: 0.00 AC: 0 AN: 48676

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.50
PhyloP100		-2.0
PromoterAI		0.062	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1830375545; hg19: chr9-139981367;