NM_058165.3:c.509C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_058165.3(MOGAT1):​c.509C>A​(p.Ser170Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000738 in 1,613,072 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (3 hom.)
• Consequence: MOGAT1 NM_058165.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007548392).
• BP6: Variant 2-222694392-C-A is Benign according to our data. Variant chr2-222694392-C-A is described in ClinVar as Benign. ClinVar VariationId is 731083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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>A	p.Ser170Tyr	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>A	p.Ser170Tyr	missense	Exon 4 of 6	ENSP00000406674.3	Q96PD6

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 608 AN: 152142 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

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: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00105 AC: 260 AN: 248066 AF XY: 0.000899

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000757

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000399 AC: 583 AN: 1460812 Hom.: 3 Cov.: 31 AF XY: 0.000347 AC XY: 252 AN XY: 726688

African (AFR) AF: 0.0146 AC: 489 AN: 33430

American (AMR) AF: 0.000829 AC: 37 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111416

Other (OTH) AF: 0.000795 AC: 48 AN: 60344

GnomAD4 genome AF: 0.00399 AC: 608 AN: 152260 Hom.: 7 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74440

African (AFR) AF: 0.0139 AC: 579 AN: 41556

American (AMR) AF: 0.00144 AC: 22 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68010

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00140 Hom.: 5

Bravo AF: 0.00452

ESP6500AA AF: 0.0127 AC: 48

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00125 AC: 151

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0075	T
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Benign	0.061	T
Sift4G	Uncertain	0.044	D
Polyphen		0.012	B
Vest4		0.54
MVP		0.80
MPC		0.031
ClinPred		0.027	T
GERP RS		4.5
Varity_R		0.31
gMVP		0.61
Mutation Taster		=92/8	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: COSV106115850; COSMIC: COSV106115850;