NM_020132.5:c.154C>G

Variant names:

• chr21-43959835-C-G
• rs201739855
• NM_020132.5:c.154C>G

Variant summary

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

The NM_020132.5(AGPAT3):​c.154C>G​(p.Arg52Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R52H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AGPAT3 NM_020132.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

Genes affected

AGPAT3 (HGNC:326): (1-acylglycerol-3-phosphate O-acyltransferase 3) The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000288593 (HGNC:):

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_020132.5. 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
	AGPAT3	NM_020132.5	MANE Select	c.154C>G	p.Arg52Gly	missense	Exon 3 of 10	NP_064517.1	Q9NRZ7-1
	AGPAT3	NM_001037553.2		c.154C>G	p.Arg52Gly	missense	Exon 2 of 9	NP_001032642.1	Q9NRZ7-1
	AGPAT3	NM_001369878.1		c.154C>G	p.Arg52Gly	missense	Exon 2 of 9	NP_001356807.1	Q9NRZ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT3	ENST00000291572.13	TSL:1 MANE Select	c.154C>G	p.Arg52Gly	missense	Exon 3 of 10	ENSP00000291572.8	Q9NRZ7-1
	AGPAT3	ENST00000327505.6	TSL:1	c.154C>G	p.Arg52Gly	missense	Exon 2 of 9	ENSP00000332989.2	Q9NRZ7-1
	AGPAT3	ENST00000398058.5	TSL:1	c.154C>G	p.Arg52Gly	missense	Exon 4 of 11	ENSP00000381135.1	Q9NRZ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458112 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725504

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50196

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111720

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.32
Sift	Benign	0.13	T
Sift4G	Benign	0.30	T
Polyphen		0.53	P
Vest4		0.90
MutPred		0.63		Loss of MoRF binding (P = 0.0083)
MVP		0.69
MPC		1.1
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.18
gMVP		0.91
Mutation Taster		=29/71	disease causing

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: rs201739855; hg19: chr21-45379716;