rs9400893

Positions:

• chr6-95590023-A-G
• chr6-95590023-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024641.4(MANEA):​c.544+3040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,852 control chromosomes in the GnomAD database, including 27,464 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 0.60 (27461 hom., cov: 31)
  • Exomes 𝑓: 0.80 (3 hom.)
• Consequence: MANEA NM_024641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

MANEA (HGNC:21072): (mannosidase endo-alpha) N-glycosylation of proteins is initiated in the endoplasmic reticulum (ER) by the transfer of the preassembled oligosaccharide glucose-3-mannose-9-N-acetylglucosamine-2 from dolichyl pyrophosphate to acceptor sites on the target protein by an oligosaccharyltransferase complex. This core oligosaccharide is sequentially processed by several ER glycosidases and by an endomannosidase (E.C. 3.2.1.130), such as MANEA, in the Golgi. MANEA catalyzes the release of mono-, di-, and triglucosylmannose oligosaccharides by cleaving the alpha-1,2-mannosidic bond that links them to high-mannose glycans (Hamilton et al., 2005 [PubMed 15677381]).[supplied by OMIM, Sep 2008]

MANEA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANEA	NM_024641.4	c.544+3040A>G		intron_variant		ENST00000358812.9	NP_078917.2
MANEA	XM_005267147.4	c.544+3040A>G		intron_variant			XP_005267204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.544+3040A>G		intron_variant		1	NM_024641.4	ENSP00000351669.4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90576 AN: 151726 Hom.: 27447 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.597 AC: 90628 AN: 151842 Hom.: 27461 Cov.: 31 AF XY: 0.595 AC XY: 44161 AN XY: 74168

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.618

Alfa AF: 0.565 Hom.: 4096

Bravo AF: 0.597

Asia WGS AF: 0.769 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9400893; hg19: chr6-96037899;