2-222671813-A-G

Position:

• chr2-222671813-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058165.3(MOGAT1):​c.28A>G​(p.Ile10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,562 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MOGAT1 NM_058165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.370

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032013685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOGAT1	NM_058165.3	c.28A>G	p.Ile10Val	missense_variant	1/6	ENST00000446656.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGAT1	ENST00000446656.4	c.28A>G	p.Ile10Val	missense_variant	1/6	5	NM_058165.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401562 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 691578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000957 AC: 1

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

Apr 09, 2024

The c.28A>G (p.I10V) alteration is located in exon 1 (coding exon 1) of the MOGAT1 gene. This alteration results from a A to G substitution at nucleotide position 28, causing the isoleucine (I) at amino acid position 10 to be replaced by a valine (V). 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	Benign	0.092
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.1
DANN	Benign	0.27
DEOGEN2	Benign	0.00070	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.050	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.38		Gain of MoRF binding (P = 0.0996);
MVP		0.14
MPC		0.018
ClinPred		0.036	T
GERP RS		-0.89
Varity_R		0.028
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: rs779344608; hg19: chr2-223536532;