Variant 11-75728131-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_025098.4(MOGAT2):c.637G>A(p.Ala213Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MOGAT2
NM_025098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.53

Variant links:

Genes affected

MOGAT2 (HGNC:23248): (monoacylglycerol O-acyltransferase 2) The protein encoded by this gene is an enzyme that catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. The encoded protein is important in the uptake of dietary fat by the small intestine. This protein forms a complex with diacylglycerol O-acyltransferase 2 in the endoplasmic reticulum, and this complex catalyzes the synthesis of triacylglycerol. [provided by RefSeq, Dec 2015]

MOGAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MOGAT2	NM_025098.4 linkuse as main transcript	c.637G>A	p.Ala213Thr	missense_variant	4/6	ENST00000198801.10	NP_079374.2
MOGAT2	XM_011545267.2 linkuse as main transcript	c.637G>A	p.Ala213Thr	missense_variant	4/6		XP_011543569.1
MOGAT2	XM_024448696.2 linkuse as main transcript	c.391G>A	p.Ala131Thr	missense_variant	4/6		XP_024304464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOGAT2	ENST00000198801.10 linkuse as main transcript	c.637G>A	p.Ala213Thr	missense_variant	4/6	1	NM_025098.4	ENSP00000198801	P1	Q3SYC2-1
MOGAT2	ENST00000526712.1 linkuse as main transcript	c.391G>A	p.Ala131Thr	missense_variant	3/5	2		ENSP00000436283		Q3SYC2-2
MOGAT2	ENST00000525093.5 linkuse as main transcript	c.637G>A	p.Ala213Thr	missense_variant, NMD_transcript_variant	4/5	2		ENSP00000436537		Q3SYC2-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152192

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248528

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134474

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460884

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.637G>A (p.A213T) alteration is located in exon 4 (coding exon 4) of the MOGAT2 gene. This alteration results from a G to A substitution at nucleotide position 637, causing the alanine (A) at amino acid position 213 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.097

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Pathogenic

4.3

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.9

D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.94

MutPred

0.93

Gain of catalytic residue at A213 (P = 0.1213);.;

MVP

0.74

MPC

0.51

ClinPred

0.98

GERP RS

5.9

Varity_R

0.92

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over