7-101198272-T-G

Variant names:

• chr7-101198272-T-G
• rs749755070
• NM_178176.4:c.587A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_178176.4(MOGAT3):​c.587A>C​(p.Glu196Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E196V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MOGAT3 NM_178176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

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.587A>C	p.Glu196Ala	missense	Exon 5 of 7	NP_835470.1	Q86VF5-1
	MOGAT3	NM_001287147.2		c.587A>C	p.Glu196Ala	missense	Exon 5 of 6	NP_001274076.1	Q86VF5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGAT3	ENST00000223114.9	TSL:1 MANE Select	c.587A>C	p.Glu196Ala	missense	Exon 5 of 7	ENSP00000223114.4	Q86VF5-1
	MOGAT3	ENST00000379423.3	TSL:1	c.587A>C	p.Glu196Ala	missense	Exon 5 of 6	ENSP00000368734.3	Q86VF5-2
	MOGAT3	ENST00000440203.6	TSL:2	c.587A>C	p.Glu196Ala	missense	Exon 5 of 6	ENSP00000403756.2	Q86VF5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459212 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725612

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110536

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.8
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.94		Loss of phosphorylation at Y199 (P = 0.103)
MVP		0.50
MPC		0.72
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.86
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs749755070; hg19: chr7-100841553;