11-75717913-A-G

Position:

• chr11-75717913-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000198801.10(MOGAT2):​c.25A>G​(p.Met9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,613,620 control chromosomes in the GnomAD database, including 158,059 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (13971 hom., cov: 33)
  • Exomes 𝑓: 0.44 (144088 hom.)
• Consequence: MOGAT2 ENST00000198801.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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]

LOC105369392 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016142428).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOGAT2	NM_025098.4	c.25A>G	p.Met9Val	missense_variant	1/6	ENST00000198801.10	NP_079374.2
LOC105369392	XR_950316.4	n.80+293T>C		intron_variant, non_coding_transcript_variant
MOGAT2	XM_011545267.2	c.25A>G	p.Met9Val	missense_variant	1/6		XP_011543569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOGAT2	ENST00000198801.10	c.25A>G	p.Met9Val	missense_variant	1/6	1	NM_025098.4	ENSP00000198801	P1
MOGAT2	ENST00000525093.5	c.25A>G	p.Met9Val	missense_variant, NMD_transcript_variant	1/5	2		ENSP00000436537

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64277 AN: 151992 Hom.: 13957 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.390 AC: 98004 AN: 250972 Hom.: 20581 AF XY: 0.397 AC XY: 53869 AN XY: 135616

Gnomad AFR exome AF: 0.427

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.384

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.439 AC: 641444 AN: 1461510 Hom.: 144088 Cov.: 47 AF XY: 0.439 AC XY: 319111 AN XY: 727012

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.423 AC: 64322 AN: 152110 Hom.: 13971 Cov.: 33 AF XY: 0.415 AC XY: 30884 AN XY: 74362

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.445

Alfa AF: 0.450 Hom.: 40232

Bravo AF: 0.420

TwinsUK AF: 0.456 AC: 1692

ALSPAC AF: 0.451 AC: 1737

ESP6500AA AF: 0.434 AC: 1908

ESP6500EA AF: 0.471 AC: 4047

ExAC AF: 0.400 AC: 48614

Asia WGS AF: 0.276 AC: 960 AN: 3478

EpiCase AF: 0.466

EpiControl AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.081
DANN	Benign	0.36
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-3.1	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.073
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.11
ClinPred		0.0035	T
GERP RS		2.8
Varity_R		0.071
gMVP		0.36

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

Other links and lift over

dbSNP: rs554202; hg19: chr11-75428958; COSMIC: COSV52219937; COSMIC: COSV52219937;