dbSNP rs9387522: MANEA:c.*654C>A (chr6-95607059-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

Publications

9 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANEA	NM_024641.4 link	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000358812.9	NP_078917.2	Q5SRI9
MANEA	XM_005267147.4 link	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5		XP_005267204.1	Q5SRI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9 link	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_024641.4	ENSP00000351669.4		Q5SRI9

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

90802

AN:

151696

Hom.:

27577

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.598

AC:

90854

AN:

151814

Hom.:

27591

Cov.:

AF XY:

0.598

AC XY:

44325

AN XY:

74184

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1778

3557

5335

7114

8892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.0

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over