rs9387522

Variant names:

• chr6-95607059-C-A
• rs9387522
• NM_024641.4:c.*654C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-95607059-C-A
• chr6-95607059-C-G
• chr6-95607059-C-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.*654C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,814 control chromosomes in the GnomAD database, including 27,591 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 (27591 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MANEA NM_024641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	NM_024641.4	MANE Select	c.*654C>A		3_prime_UTR	Exon 5 of 5	NP_078917.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.*654C>A		3_prime_UTR	Exon 5 of 5	ENSP00000351669.4	Q5SRI9
	MANEA	ENST00000682663.1		c.*654C>A		3_prime_UTR	Exon 5 of 5	ENSP00000507267.1	Q5SRI9
	MANEA	ENST00000684753.1		c.*654C>A		3_prime_UTR	Exon 5 of 5	ENSP00000506887.1	Q5SRI9

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90802 AN: 151696 Hom.: 27577 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.615

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.598 AC: 90854 AN: 151814 Hom.: 27591 Cov.: 31 AF XY: 0.598 AC XY: 44325 AN XY: 74184

African (AFR) AF: 0.623 AC: 25805 AN: 41440

American (AMR) AF: 0.533 AC: 8123 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4485 AN: 5168

South Asian (SAS) AF: 0.733 AC: 3525 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5649 AN: 10506

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39206 AN: 67876

Other (OTH) AF: 0.618 AC: 1306 AN: 2112

Alfa AF: 0.578 Hom.: 10458

Bravo AF: 0.597

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9387522; hg19: chr6-96054935;