2-222694392-C-T

Variant names:

• chr2-222694392-C-T
• rs142425542
• NM_058165.3:c.509C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058165.3(MOGAT1):​c.509C>T​(p.Ser170Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S170Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGAT1 NM_058165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 3 publications found

Genes affected

MOGAT1 (HGNC:18210): (monoacylglycerol O-acyltransferase 1) Acyl-CoA:monoacylglycerol acyltransferase (MOGAT; EC 2.3.1.22) catalyzes the synthesis of diacylglycerols, the precursor of physiologically important lipids such as triacylglycerol and phospholipids (Yen et al., 2002 [PubMed 12077311]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058165.3. 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
	MOGAT1	NM_058165.3	MANE Select	c.509C>T	p.Ser170Phe	missense	Exon 4 of 6	NP_477513.2	Q96PD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGAT1	ENST00000446656.4	TSL:5 MANE Select	c.509C>T	p.Ser170Phe	missense	Exon 4 of 6	ENSP00000406674.3	Q96PD6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.2
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.034	D
Polyphen		0.56	P
Vest4		0.54
MutPred		0.41		Loss of disorder (P = 1e-04)
MVP		0.87
MPC		0.13
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.51
gMVP		0.58
Mutation Taster		=88/12	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: rs142425542; hg19: chr2-223559111; COSMIC: COSV71479831; COSMIC: COSV71479831;