rs5860729

Positions:

• chr4-102632290-GAA-G
• chr4-102632290-GAA-GA
• chr4-102632290-GAA-GAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_005908.4(MANBA):​c.2416-11_2416-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,389,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: MANBA NM_005908.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.248

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-102632290-GAA-G is Benign according to our data. Variant chr4-102632290-GAA-G is described in ClinVar as [Benign]. Clinvar id is 1639188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000748 (111/148450) while in subpopulation AFR AF= 0.00251 (102/40718). AF 95% confidence interval is 0.00211. There are 0 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.2416-11_2416-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.2341-11_2341-10del		splice_polypyrimidine_tract_variant, intron_variant
MANBA	XM_047415693.1	c.2341-11_2341-10del		splice_polypyrimidine_tract_variant, intron_variant
MANBA	XM_047415694.1	c.1768-11_1768-10del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.2416-11_2416-10del		splice_polypyrimidine_tract_variant, intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.000742 AC: 110 AN: 148344 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000333

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000328 AC: 407 AN: 1240772 Hom.: 0 AF XY: 0.000305 AC XY: 190 AN XY: 622834

Gnomad4 AFR exome AF: 0.00225

Gnomad4 AMR exome AF: 0.000169

Gnomad4 ASJ exome AF: 0.0000429

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.000271

Gnomad4 FIN exome AF: 0.0000412

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.000307

GnomAD4 genome AF: 0.000748 AC: 111 AN: 148450 Hom.: 0 Cov.: 0 AF XY: 0.000775 AC XY: 56 AN XY: 72282

Gnomad4 AFR AF: 0.00251

Gnomad4 AMR AF: 0.000333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000258 Hom.: 1436

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beta-D-mannosidosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs5860729; hg19: chr4-103553447;