chr21-43959835-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT3	NM_020132.5	c.154C>G	p.Arg52Gly	missense_variant	Exon 3 of 10	ENST00000291572.13	NP_064517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPAT3	ENST00000291572.13	c.154C>G	p.Arg52Gly	missense_variant	Exon 3 of 10	1	NM_020132.5	ENSP00000291572.8
ENSG00000288593	ENST00000674444.1	c.*162C>G		downstream_gene_variant				ENSP00000501503.1

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

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;T;T;T;T;.;.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.98	.;D;.;.;D;.;.;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.8	M;.;M;M;.;M;M;.;.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.4	N;D;N;N;D;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.13	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.30	T;D;T;T;D;T;T;T;T;T
Polyphen		0.53	P;.;P;P;.;P;P;.;.;P
Vest4		0.90
MutPred		0.63		Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-45379716;