Genetic Variant MOGAT3:p.Leu166Pro (chr7-101198362-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_178176.4(MOGAT3):c.497T>C(p.Leu166Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 1,542,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

MOGAT3
NM_178176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

Variant links:

Genes affected

MOGAT3 (HGNC:23249): (monoacylglycerol O-acyltransferase 3) Acyl-CoA:monoacylglycerol acyltransferase (MOGAT; EC 2.3.1.22) catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA (Cheng et al., 2003 [PubMed 12618427]).[supplied by OMIM, Mar 2008]

MOGAT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178176.4. 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
	MOGAT3	NM_178176.4	MANE Select	c.497T>C	p.Leu166Pro	missense	Exon 5 of 7	NP_835470.1	Q86VF5-1
	MOGAT3	NM_001287147.2		c.497T>C	p.Leu166Pro	missense	Exon 5 of 6	NP_001274076.1	Q86VF5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOGAT3	ENST00000223114.9	TSL:1 MANE Select	c.497T>C	p.Leu166Pro	missense	Exon 5 of 7	ENSP00000223114.4	Q86VF5-1
MOGAT3	ENST00000379423.3	TSL:1	c.497T>C	p.Leu166Pro	missense	Exon 5 of 6	ENSP00000368734.3	Q86VF5-2
MOGAT3	ENST00000440203.6	TSL:2	c.497T>C	p.Leu166Pro	missense	Exon 5 of 6	ENSP00000403756.2	Q86VF5-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000870

AC:

AN:

195514

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000280

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000987

Gnomad OTH exome

AF:

0.000218

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1390482

Hom.:

Cov.:

AF XY:

0.0000366

AC XY:

AN XY:

683534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31310

American (AMR)

AF:

0.000204

AC:

AN:

34292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21674

East Asian (EAS)

AF:

0.00

AC:

AN:

38866

South Asian (SAS)

AF:

0.00

AC:

AN:

75774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50878

Middle Eastern (MID)

AF:

0.000370

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

0.0000363

AC:

AN:

1075148

Other (OTH)

AF:

0.0000525

AC:

AN:

57136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000661

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

1.8

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.27

Sift

Uncertain

0.013

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.81

MVP

0.25

MPC

0.86

ClinPred

0.70

GERP RS

1.2

Varity_R

0.37

gMVP

0.80

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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