chr7-101196059-C-G

Variant names:

• chr7-101196059-C-G
• rs371428887
• NM_178176.4:c.913G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178176.4(MOGAT3):​c.913G>C​(p.Glu305Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,016 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. E305K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MOGAT3 NM_178176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 6 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_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=0.03481087).

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.913G>C	p.Glu305Gln	missense	Exon 7 of 7	NP_835470.1	Q86VF5-1
	MOGAT3	NM_001287147.2		c.710G>C	p.Arg237Pro	missense	Exon 6 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.913G>C	p.Glu305Gln	missense	Exon 7 of 7	ENSP00000223114.4	Q86VF5-1
	MOGAT3	ENST00000379423.3	TSL:1	c.710G>C	p.Arg237Pro	missense	Exon 6 of 6	ENSP00000368734.3	Q86VF5-2
	MOGAT3	ENST00000893927.1		c.805G>C	p.Glu269Gln	missense	Exon 6 of 6	ENSP00000563986.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248398 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460016 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726324

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000448 AC: 2 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110928

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.063
DANN	Benign	0.046
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.63
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.0030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.055	B
Vest4		0.086
MutPred		0.36		Loss of disorder (P = 0.1558)
MVP		0.12
MPC		0.22
ClinPred		0.034	T
GERP RS		-3.5
Varity_R		0.094
gMVP		0.31
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs371428887; hg19: chr7-100839340;