rs11553430

Variant names:

• chr6-32168994-C-T
• rs11553430
• NM_006411.4:c.*282G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006411.4(AGPAT1):​c.*282G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 507,700 control chromosomes in the GnomAD database, including 104 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 0.015 (30 hom., cov: 32)
  • Exomes 𝑓: 0.016 (74 hom.)
• Consequence: AGPAT1 NM_006411.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 6 publications found

Genes affected

AGPAT1 (HGNC:324): (1-acylglycerol-3-phosphate O-acyltransferase 1) This gene encodes an enzyme that converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA and PA are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. This enzyme localizes to the endoplasmic reticulum. This gene is located in the class III region of the human major histocompatibility complex. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0151 (2289/152074) while in subpopulation NFE AF = 0.0246 (1672/67966). AF 95% confidence interval is 0.0236. There are 30 homozygotes in GnomAd4. There are 1077 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006411.4. 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
	AGPAT1	NM_006411.4	MANE Select	c.*282G>A		3_prime_UTR	Exon 7 of 7	NP_006402.1	A0A024RCV5
	AGPAT1	NM_001371437.1		c.*282G>A		3_prime_UTR	Exon 7 of 7	NP_001358366.1
	AGPAT1	NM_001371438.1		c.*282G>A		3_prime_UTR	Exon 7 of 7	NP_001358367.1	Q99943

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT1	ENST00000375107.8	TSL:1 MANE Select	c.*282G>A		3_prime_UTR	Exon 7 of 7	ENSP00000364248.3	Q99943
	AGPAT1	ENST00000336984.6	TSL:1	c.*282G>A		3_prime_UTR	Exon 7 of 7	ENSP00000337463.6	Q99943
	PPT2-EGFL8	ENST00000422437.5	TSL:5	n.*1379-299C>T		intron	N/A	ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2289 AN: 151956 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0163 AC: 5788 AN: 355626 Hom.: 74 Cov.: 0 AF XY: 0.0155 AC XY: 2853 AN XY: 183702

African (AFR) AF: 0.00385 AC: 43 AN: 11182

American (AMR) AF: 0.00768 AC: 118 AN: 15358

Ashkenazi Jewish (ASJ) AF: 0.00480 AC: 56 AN: 11672

East Asian (EAS) AF: 0.00 AC: 0 AN: 27126

South Asian (SAS) AF: 0.000428 AC: 12 AN: 28070

European-Finnish (FIN) AF: 0.0187 AC: 444 AN: 23768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1654

European-Non Finnish (NFE) AF: 0.0224 AC: 4829 AN: 215222

Other (OTH) AF: 0.0133 AC: 286 AN: 21574

GnomAD4 genome AF: 0.0151 AC: 2289 AN: 152074 Hom.: 30 Cov.: 32 AF XY: 0.0145 AC XY: 1077 AN XY: 74348

African (AFR) AF: 0.00429 AC: 178 AN: 41470

American (AMR) AF: 0.0129 AC: 197 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.0188 AC: 199 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1672 AN: 67966

Other (OTH) AF: 0.0138 AC: 29 AN: 2106

Alfa AF: 0.0213 Hom.: 49

Bravo AF: 0.0137

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11553430; hg19: chr6-32136771;