rs1345228065

Positions:

• chr4-102632289-AG-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005908.4(MANBA):​c.2416-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000096 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MANBA NM_005908.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 4-102632289-AG-A is Benign according to our data. Variant chr4-102632289-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 542168.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.2416-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.2341-9del		splice_polypyrimidine_tract_variant, intron_variant
MANBA	XM_047415693.1	c.2341-9del		splice_polypyrimidine_tract_variant, intron_variant
MANBA	XM_047415694.1	c.1768-9del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.2416-9del		splice_polypyrimidine_tract_variant, intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 103810 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000141 AC: 201 AN: 1428516 Hom.: 0 Cov.: 25 AF XY: 0.000135 AC XY: 96 AN XY: 712648

Gnomad4 AFR exome AF: 0.000888

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000281

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000591

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000963 AC: 1 AN: 103810 Hom.: 0 Cov.: 29 AF XY: 0.0000198 AC XY: 1 AN XY: 50572

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000123

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000963 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beta-D-mannosidosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1345228065; hg19: chr4-103553446;