rs9400893

Variant names:

• chr6-95590023-A-G
• rs9400893
• NM_024641.4:c.544+3040A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	NM_024641.4	MANE Select	c.544+3040A>G		intron	N/A	NP_078917.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.544+3040A>G		intron	N/A	ENSP00000351669.4
	MANEA	ENST00000474553.1	TSL:5	n.64A>G		non_coding_transcript_exon	Exon 2 of 5
	MANEA	ENST00000682663.1		c.544+3040A>G		intron	N/A	ENSP00000507267.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.622 AC: 25770 AN: 41406

American (AMR) AF: 0.532 AC: 8111 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3468

East Asian (EAS) AF: 0.867 AC: 4461 AN: 5148

South Asian (SAS) AF: 0.731 AC: 3514 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5579 AN: 10534

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39138 AN: 67932

Other (OTH) AF: 0.618 AC: 1301 AN: 2104

Alfa AF: 0.567 Hom.: 4244

Bravo AF: 0.597

Asia WGS AF: 0.769 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9400893; hg19: chr6-96037899;