9-137099733-C-A

Variant names:

• chr9-137099733-C-A
• rs145906530
• NM_016219.5:c.768C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016219.5(MAN1B1):​c.768C>A​(p.Val256Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V256V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAN1B1 NM_016219.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• 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 Gene-Disease associations (from GenCC):

• MAN1B1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Rafiq syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.015).
• BP7: Synonymous conserved (PhyloP=-0.536 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1B1	NM_016219.5	MANE Select	c.768C>A	p.Val256Val	synonymous	Exon 6 of 13	NP_057303.2	Q9UKM7
	MAN1B1	NR_045720.2		n.783C>A		non_coding_transcript_exon	Exon 6 of 13
	MAN1B1	NR_045721.2		n.914C>A		non_coding_transcript_exon	Exon 7 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1B1	ENST00000371589.9	TSL:1 MANE Select	c.768C>A	p.Val256Val	synonymous	Exon 6 of 13	ENSP00000360645.4	Q9UKM7
	MAN1B1	ENST00000371587.9	TSL:1	n.*470C>A		non_coding_transcript_exon	Exon 7 of 14	ENSP00000483132.2	A0A087X064
	MAN1B1	ENST00000544448.6	TSL:1	n.768C>A		non_coding_transcript_exon	Exon 6 of 13	ENSP00000444966.2	H0YGV7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs145906530; hg19: chr9-139994185;