rs747425990

Variant names:

• chr21-43969268-G-A
• rs747425990
• NM_020132.5:c.499G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-43969268-G-A
• chr21-43969268-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020132.5(AGPAT3):​c.499G>A​(p.Glu167Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: AGPAT3 NM_020132.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51
• Publications: 2 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

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.499G>A	p.Glu167Lys	missense	Exon 5 of 10	NP_064517.1	Q9NRZ7-1
	AGPAT3	NM_001037553.2		c.499G>A	p.Glu167Lys	missense	Exon 4 of 9	NP_001032642.1	Q9NRZ7-1
	AGPAT3	NM_001369878.1		c.499G>A	p.Glu167Lys	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.499G>A	p.Glu167Lys	missense	Exon 5 of 10	ENSP00000291572.8	Q9NRZ7-1
	AGPAT3	ENST00000327505.6	TSL:1	c.499G>A	p.Glu167Lys	missense	Exon 4 of 9	ENSP00000332989.2	Q9NRZ7-1
	AGPAT3	ENST00000398058.5	TSL:1	c.499G>A	p.Glu167Lys	missense	Exon 6 of 11	ENSP00000381135.1	Q9NRZ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727236

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.68	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.20	T
Polyphen		0.70	P
Vest4		0.57
MutPred		0.56		Gain of ubiquitination at E167 (P = 0.0592)
MVP		0.84
MPC		2.0
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.50
gMVP		0.95
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs747425990; hg19: chr21-45389149; COSMIC: COSV52370402; COSMIC: COSV52370402;