21-43969224-G-A

Variant names:

• chr21-43969224-G-A
• rs368657540
• NM_020132.5:c.455G>A

Variant summary

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

The NM_020132.5(AGPAT3):​c.455G>A​(p.Arg152Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: AGPAT3 NM_020132.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31
• Publications: 1 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]

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.455G>A	p.Arg152Gln	missense	Exon 5 of 10	NP_064517.1	Q9NRZ7-1
	AGPAT3	NM_001037553.2		c.455G>A	p.Arg152Gln	missense	Exon 4 of 9	NP_001032642.1	Q9NRZ7-1
	AGPAT3	NM_001369878.1		c.455G>A	p.Arg152Gln	missense	Exon 4 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.455G>A	p.Arg152Gln	missense	Exon 5 of 10	ENSP00000291572.8	Q9NRZ7-1
	AGPAT3	ENST00000327505.6	TSL:1	c.455G>A	p.Arg152Gln	missense	Exon 4 of 9	ENSP00000332989.2	Q9NRZ7-1
	AGPAT3	ENST00000398058.5	TSL:1	c.455G>A	p.Arg152Gln	missense	Exon 6 of 11	ENSP00000381135.1	Q9NRZ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251424 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000150 AC: 22 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	0.31	N
PhyloP100		5.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.024	D
Polyphen		0.64	P
Vest4		0.25
MVP		0.71
MPC		1.1
ClinPred		0.30	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.87
Mutation Taster		=63/37	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: rs368657540; hg19: chr21-45389105;