dbSNP rs9400893: MANEA:c.544+3040A>G (chr6-95590023-A-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

7 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:

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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=-0.92).

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 rank	MANE	Protein	UniProt
MANEA	NM_024641.4 link	c.544+3040A>G		intron_variant	Intron 2 of 4	ENST00000358812.9	NP_078917.2	Q5SRI9
MANEA	XM_005267147.4 link	c.544+3040A>G		intron_variant	Intron 2 of 4		XP_005267204.1	Q5SRI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9 link	c.544+3040A>G		intron_variant	Intron 2 of 4	1	NM_024641.4	ENSP00000351669.4		Q5SRI9

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90576

AN:

151726

Hom.:

27447

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

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:

0.833

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.597

AC:

90628

AN:

151842

Hom.:

27461

Cov.:

AF XY:

0.595

AC XY:

44161

AN XY:

74168

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1803

3606

5409

7212

9015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.567

Hom.:

4244

Bravo

AF:

0.597

Asia WGS

AF:

0.769

AC:

2674

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

(source)

DANN

Benign

0.59

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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