rs3734462

Positions:

• chr6-161136630-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020133.3(AGPAT4):​c.1047C>T​(p.Ser349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,612,954 control chromosomes in the GnomAD database, including 30,593 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2298 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28295 hom.)
• Consequence: AGPAT4 NM_020133.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

AGPAT4 (HGNC:20885): (1-acylglycerol-3-phosphate O-acyltransferase 4) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.053 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT4	NM_020133.3	c.1047C>T	p.Ser349=	synonymous_variant	9/9	ENST00000320285.9	NP_064518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT4	ENST00000320285.9	c.1047C>T	p.Ser349=	synonymous_variant	9/9	1	NM_020133.3	ENSP00000314036	P1
AGPAT4	ENST00000366911.9	c.*520C>T		3_prime_UTR_variant	8/8	1		ENSP00000355878

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22967 AN: 152122 Hom.: 2293 Cov.: 33

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.191 AC: 47546 AN: 248986 Hom.: 6139 AF XY: 0.178 AC XY: 23935 AN XY: 134808

Gnomad AFR exome AF: 0.0434

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.0581

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.186 AC: 271511 AN: 1460714 Hom.: 28295 Cov.: 32 AF XY: 0.181 AC XY: 131396 AN XY: 726716

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.151 AC: 22986 AN: 152240 Hom.: 2298 Cov.: 33 AF XY: 0.150 AC XY: 11146 AN XY: 74434

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.142

Alfa AF: 0.178 Hom.: 4378

Bravo AF: 0.163

Asia WGS AF: 0.0930 AC: 324 AN: 3478

EpiCase AF: 0.175

EpiControl AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3734462; hg19: chr6-161557662; COSMIC: COSV57246080;