NM_005908.4:c.549+3126G>A

Variant names:

• chr4-102719745-C-T
• rs10489108
• NM_005908.4:c.549+3126G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005908.4(MANBA):​c.549+3126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,274 control chromosomes in the GnomAD database, including 747 homozygotes. 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: 𝑓 0.058 (747 hom., cov: 32)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 1 publications found

Genes affected

MANBA (HGNC:6831): (mannosidase beta) This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]

MANBA Gene-Disease associations (from GenCC):

• beta-mannosidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005908.4. 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
	MANBA	NM_005908.4	MANE Select	c.549+3126G>A		intron	N/A	NP_005899.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	ENST00000647097.2	MANE Select	c.549+3126G>A		intron	N/A	ENSP00000495247.1	O00462
	MANBA	ENST00000642252.1		c.549+3126G>A		intron	N/A	ENSP00000495483.1	A0A2R8YEC9
	MANBA	ENST00000954426.1		c.549+3126G>A		intron	N/A	ENSP00000624485.1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8786 AN: 152158 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00756

Gnomad OTH AF: 0.0455

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0579 AC: 8814 AN: 152274 Hom.: 747 Cov.: 32 AF XY: 0.0564 AC XY: 4197 AN XY: 74468

African (AFR) AF: 0.187 AC: 7745 AN: 41528

American (AMR) AF: 0.0254 AC: 389 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4832

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00756 AC: 514 AN: 68022

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.0377 Hom.: 64

Bravo AF: 0.0663

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.42
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10489108; hg19: chr4-103640902;