rs408359

Positions:

• chr6-32174106-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006411.4(AGPAT1):​c.-10+1708C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,132 control chromosomes in the GnomAD database, including 1,599 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 0.12 (1599 hom., cov: 32)
• Consequence: AGPAT1 NM_006411.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPAT1	NM_006411.4	c.-10+1708C>T		intron_variant		ENST00000375107.8
AGPAT1	NM_001371437.1	c.3+2404C>T		intron_variant
AGPAT1	NM_001371438.1	c.-9-2601C>T		intron_variant
AGPAT1	NM_032741.5	c.-9-2601C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT1	ENST00000375107.8	c.-10+1708C>T		intron_variant		1	NM_006411.4	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152012 Hom.: 1593 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 18948 AN: 152132 Hom.: 1599 Cov.: 32 AF XY: 0.127 AC XY: 9458 AN XY: 74368

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.0456

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0912 Hom.: 1521

Bravo AF: 0.130

Asia WGS AF: 0.243 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs408359; hg19: chr6-32141883;