Genetic Variant NM_024641.4:c.*307C>T (chr6-95606712-C-T) – 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.*307C>T 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 166,386 control chromosomes in the GnomAD database, including 30,217 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 ( 27554 hom., cov: 31)

Exomes 𝑓: 0.59 ( 2663 hom. )

Consequence

MANEA
NM_024641.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

13 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 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.*307C>T		3_prime_UTR	Exon 5 of 5	NP_078917.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MANEA	ENST00000358812.9	TSL:1 MANE Select	c.*307C>T	3_prime_UTR	Exon 5 of 5	ENSP00000351669.4	Q5SRI9
MANEA	ENST00000682663.1		c.*307C>T	3_prime_UTR	Exon 5 of 5	ENSP00000507267.1	Q5SRI9
MANEA	ENST00000684753.1		c.*307C>T	3_prime_UTR	Exon 5 of 5	ENSP00000506887.1	Q5SRI9

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90721

AN:

151654

Hom.:

27540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.616

GnomAD4 exome

AF:

0.594

AC:

8687

AN:

14614

Hom.:

2663

Cov.:

AF XY:

0.588

AC XY:

4703

AN XY:

8000

show subpopulations

African (AFR)

AF:

0.613

AC:

260

AN:

424

American (AMR)

AF:

0.497

AC:

442

AN:

890

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

266

AN:

464

East Asian (EAS)

AF:

0.827

AC:

915

AN:

1106

South Asian (SAS)

AF:

0.684

AC:

405

AN:

592

European-Finnish (FIN)

AF:

0.523

AC:

201

AN:

384

Middle Eastern (MID)

AF:

0.581

AC:

AN:

European-Non Finnish (NFE)

AF:

0.573

AC:

5698

AN:

9950

Other (OTH)

AF:

0.625

AC:

464

AN:

742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

172

344

515

687

859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.598

AC:

90773

AN:

151772

Hom.:

27554

Cov.:

AF XY:

0.597

AC XY:

44279

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.622

AC:

25777

AN:

41430

American (AMR)

AF:

0.533

AC:

8121

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

2063

AN:

3464

East Asian (EAS)

AF:

0.867

AC:

4469

AN:

5154

South Asian (SAS)

AF:

0.732

AC:

3523

AN:

4810

European-Finnish (FIN)

AF:

0.537

AC:

5644

AN:

10514

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39180

AN:

67858

Other (OTH)

AF:

0.620

AC:

1306

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1817

3633

5450

7266

9083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.586

Hom.:

7260

Bravo

AF:

0.597

Asia WGS

AF:

0.777

AC:

2674

AN:

3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.8

(source)

DANN

Benign

0.61

PhyloP100

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over