Genetic Variant MANEA:c.-169G>T (chr6-95577508-G-T) – 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.-169G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,148 control chromosomes in the GnomAD database, including 28,134 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 ( 28114 hom., cov: 34)

Exomes 𝑓: 0.64 ( 20 hom. )

Consequence

MANEA
ENST00000369293.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

Publications

8 publications found

Variant links:

COSMIC-nc: COSV62589654

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:

MANEA-DT (HGNC:43732): (MANEA divergent transcript)

MANEA-DT 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=-0.78).

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: ENST00000369293.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MANEA	NM_024641.4	MANE Select	c.-169G>T	upstream_gene	N/A	NP_078917.2
MANEA-DT	NR_047502.1		n.-57C>A	upstream_gene	N/A
MANEA-DT	NR_104136.1		n.-57C>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MANEA	ENST00000369293.6	TSL:1	c.-169G>T	5_prime_UTR	Exon 1 of 2	ENSP00000358299.1	X6R7A2
MANEA-DT	ENST00000791249.1		n.64+122C>A	intron	N/A
MANEA	ENST00000358812.9	TSL:1 MANE Select	c.-169G>T	upstream_gene	N/A	ENSP00000351669.4	Q5SRI9

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91701

AN:

151944

Hom.:

28103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.622

GnomAD4 exome

AF:

0.635

AC:

AN:

Hom.:

Cov.:

AF XY:

0.611

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.646

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.603

AC:

91748

AN:

152052

Hom.:

28114

Cov.:

AF XY:

0.601

AC XY:

44726

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.642

AC:

26663

AN:

41514

American (AMR)

AF:

0.536

AC:

8199

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2067

AN:

3472

East Asian (EAS)

AF:

0.867

AC:

4472

AN:

5158

South Asian (SAS)

AF:

0.734

AC:

3544

AN:

4826

European-Finnish (FIN)

AF:

0.529

AC:

5585

AN:

10550

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39212

AN:

67936

Other (OTH)

AF:

0.625

AC:

1317

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1951

3903

5854

7806

9757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.576

Hom.:

3164

Bravo

AF:

0.604

Asia WGS

AF:

0.773

AC:

2677

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.9

(source)

DANN

Benign

0.65

PhyloP100

0.40

PromoterAI

-0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over