dbSNP rs9374586: MANEA:c.*263T>C (chr6-95587299-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000369293.6(MANEA):c.*263T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 302,378 control chromosomes in the GnomAD database, including 57,295 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 0.65 ( 32168 hom., cov: 31)

Exomes 𝑓: 0.57 ( 25127 hom. )

Consequence

MANEA
ENST00000369293.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

11 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANEA	NM_024641.4 link	c.544+316T>C		intron_variant	Intron 2 of 4	ENST00000358812.9	NP_078917.2	Q5SRI9
MANEA	XM_005267147.4 link	c.544+316T>C		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+316T>C		intron_variant	Intron 2 of 4	1	NM_024641.4	ENSP00000351669.4		Q5SRI9

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98248

AN:

151742

Hom.:

32156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.670

GnomAD4 exome

AF:

0.574

AC:

86335

AN:

150518

Hom.:

25127

Cov.:

AF XY:

0.576

AC XY:

44586

AN XY:

77454

show subpopulations

African (AFR)

AF:

0.635

AC:

2742

AN:

4320

American (AMR)

AF:

0.498

AC:

3164

AN:

6356

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2837

AN:

4898

East Asian (EAS)

AF:

0.772

AC:

6539

AN:

8474

South Asian (SAS)

AF:

0.672

AC:

5900

AN:

8778

European-Finnish (FIN)

AF:

0.526

AC:

10461

AN:

19872

Middle Eastern (MID)

AF:

0.579

AC:

368

AN:

636

European-Non Finnish (NFE)

AF:

0.557

AC:

49283

AN:

88462

Other (OTH)

AF:

0.578

AC:

5041

AN:

8722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

1485

2970

4456

5941

7426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.647

AC:

98307

AN:

151860

Hom.:

32168

Cov.:

AF XY:

0.645

AC XY:

47807

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.690

AC:

28586

AN:

41442

American (AMR)

AF:

0.575

AC:

8758

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

2269

AN:

3470

East Asian (EAS)

AF:

0.867

AC:

4474

AN:

5160

South Asian (SAS)

AF:

0.741

AC:

3561

AN:

4808

European-Finnish (FIN)

AF:

0.551

AC:

5791

AN:

10508

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42629

AN:

67920

Other (OTH)

AF:

0.673

AC:

1420

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1757

3514

5272

7029

8786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.634

Hom.:

35098

Bravo

AF:

0.650

Asia WGS

AF:

0.786

AC:

2730

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.19

(source)

DANN

Benign

0.75

PhyloP100

-1.7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over