Genetic Variant MANEAL:p.Asp79Gly (chr1-37794418-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001113482.2(MANEAL):c.236A>G(p.Asp79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 147,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D79A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.528

Publications

0 publications found

Variant links:

Genes affected

MANEAL (HGNC:26452): (mannosidase endo-alpha like) Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

MANEAL links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049678862).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113482.2. 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
	MANEAL	NM_001113482.2	MANE Select	c.236A>G	p.Asp79Gly	missense	Exon 1 of 4	NP_001106954.1	Q5VSG8-1
	MANEAL	NM_001031740.3		c.236A>G	p.Asp79Gly	missense	Exon 1 of 4	NP_001026910.1	Q5VSG8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MANEAL	ENST00000373045.11	TSL:1 MANE Select	c.236A>G	p.Asp79Gly	missense	Exon 1 of 4	ENSP00000362136.6	Q5VSG8-1
MANEAL	ENST00000397631.7	TSL:1	c.236A>G	p.Asp79Gly	missense	Exon 1 of 4	ENSP00000380755.3	Q5VSG8-3
MANEAL	ENST00000951301.1		c.236A>G	p.Asp79Gly	missense	Exon 1 of 5	ENSP00000621360.1

Frequencies

GnomAD3 genomes

AF:

0.00000676

AC:

AN:

147886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1209540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

588290

African (AFR)

AF:

0.00

AC:

AN:

25464

American (AMR)

AF:

0.00

AC:

AN:

22674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19794

East Asian (EAS)

AF:

0.00

AC:

AN:

27378

South Asian (SAS)

AF:

0.00

AC:

AN:

52778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

975194

Other (OTH)

AF:

0.00

AC:

AN:

48468

GnomAD4 genome

AF:

0.00000676

AC:

AN:

147886

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40518

American (AMR)

AF:

0.00

AC:

AN:

14954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.000201

AC:

AN:

4978

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66740

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.36

M_CAP

Benign

0.019

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.53

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.85

REVEL

Benign

0.085

Sift

Benign

0.28

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.045

MutPred

0.12

Gain of methylation at R76 (P = 0.0585)

MVP

0.061

MPC

1.4

ClinPred

0.10

GERP RS

0.88

PromoterAI

0.14

Neutral

(source)

Varity_R

0.044

gMVP

0.56

Mutation Taster

=94/6

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over