rs3734462

Variant names:

• chr6-161136630-G-A
• rs3734462
• NM_020133.3:c.1047C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020133.3(AGPAT4):​c.1047C>T​(p.Ser349Ser) 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. Synonymous variant affecting the same amino acid position (i.e. S349S) has been classified as Uncertain significance.

• 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020133.3. 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
	AGPAT4	NM_020133.3	MANE Select	c.1047C>T	p.Ser349Ser	synonymous	Exon 9 of 9	NP_064518.1	Q9NRZ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT4	ENST00000320285.9	TSL:1 MANE Select	c.1047C>T	p.Ser349Ser	synonymous	Exon 9 of 9	ENSP00000314036.4	Q9NRZ5-1
	AGPAT4	ENST00000860938.1		c.1047C>T	p.Ser349Ser	synonymous	Exon 9 of 9	ENSP00000530997.1
	AGPAT4	ENST00000928275.1		c.1047C>T	p.Ser349Ser	synonymous	Exon 9 of 9	ENSP00000598334.1

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

GnomAD2 exomes AF: 0.191 AC: 47546 AN: 248986 AF XY: 0.178

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 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

African (AFR) AF: 0.0365 AC: 1221 AN: 33474

American (AMR) AF: 0.402 AC: 17977 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2799 AN: 26132

East Asian (EAS) AF: 0.191 AC: 7574 AN: 39692

South Asian (SAS) AF: 0.0607 AC: 5239 AN: 86246

European-Finnish (FIN) AF: 0.157 AC: 8387 AN: 53346

Middle Eastern (MID) AF: 0.0541 AC: 312 AN: 5766

European-Non Finnish (NFE) AF: 0.196 AC: 218244 AN: 1110974

Other (OTH) AF: 0.162 AC: 9758 AN: 60364

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

African (AFR) AF: 0.0440 AC: 1830 AN: 41558

American (AMR) AF: 0.293 AC: 4477 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1023 AN: 5152

South Asian (SAS) AF: 0.0627 AC: 303 AN: 4832

European-Finnish (FIN) AF: 0.157 AC: 1667 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12896 AN: 68012

Other (OTH) AF: 0.142 AC: 300 AN: 2116

Alfa AF: 0.177 Hom.: 5315

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		-0.053
Mutation Taster		=91/9	polymorphism (auto)

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