chr21-43980993-C-T

Variant names:

• chr21-43980993-C-T
• rs763827550
• NM_020132.5:c.848C>T

Variant summary

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

The NM_020132.5(AGPAT3):​c.848C>T​(p.Ala283Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: AGPAT3 NM_020132.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46
• 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.848C>T	p.Ala283Val	missense	Exon 9 of 10	NP_064517.1	Q9NRZ7-1
	AGPAT3	NM_001037553.2		c.848C>T	p.Ala283Val	missense	Exon 8 of 9	NP_001032642.1	Q9NRZ7-1
	AGPAT3	NM_001369878.1		c.848C>T	p.Ala283Val	missense	Exon 8 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.848C>T	p.Ala283Val	missense	Exon 9 of 10	ENSP00000291572.8	Q9NRZ7-1
	AGPAT3	ENST00000327505.6	TSL:1	c.848C>T	p.Ala283Val	missense	Exon 8 of 9	ENSP00000332989.2	Q9NRZ7-1
	AGPAT3	ENST00000398058.5	TSL:1	c.848C>T	p.Ala283Val	missense	Exon 10 of 11	ENSP00000381135.1	Q9NRZ7-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251382 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461784 Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17 AN XY: 727204

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111938

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74302

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.10
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.086
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.22
Sift	Benign	0.11	T
Sift4G	Benign	0.27	T
Polyphen		0.24	B
Vest4		0.72
MutPred		0.39		Loss of disorder (P = 0.0912)
MVP		0.16
MPC		0.89
ClinPred		0.62	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.75
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763827550; hg19: chr21-45400874;