2-222689315-T-A

Position:

• chr2-222689315-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058165.3(MOGAT1):​c.324T>A​(p.Phe108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: MOGAT1 NM_058165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOGAT1	NM_058165.3	c.324T>A	p.Phe108Leu	missense_variant	3/6	ENST00000446656.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGAT1	ENST00000446656.4	c.324T>A	p.Phe108Leu	missense_variant	3/6	5	NM_058165.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74396

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.324T>A (p.F108L) alteration is located in exon 3 (coding exon 3) of the MOGAT1 gene. This alteration results from a T to A substitution at nucleotide position 324, causing the phenylalanine (F) at amino acid position 108 to be replaced by a leucine (L). 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	0.82
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.21
Sift	Uncertain	0.028	D
Sift4G	Benign	0.14	T
Polyphen		0.028	B
Vest4		0.49
MutPred		0.72		Gain of sheet (P = 0.1451);
MVP		0.30
MPC		0.023
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.51
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1487476755; hg19: chr2-223554034;