rs408359

Variant names:

• chr6-32174106-G-A
• rs408359
• NM_006411.4:c.-10+1708C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT1	NM_006411.4	MANE Select	c.-10+1708C>T		intron	N/A	NP_006402.1
	AGPAT1	NM_001371437.1		c.3+2404C>T		intron	N/A	NP_001358366.1
	AGPAT1	NM_001371438.1		c.-9-2601C>T		intron	N/A	NP_001358367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT1	ENST00000375107.8	TSL:1 MANE Select	c.-10+1708C>T		intron	N/A	ENSP00000364248.3
	AGPAT1	ENST00000336984.6	TSL:1	c.-9-2601C>T		intron	N/A	ENSP00000337463.6
	AGPAT1	ENST00000375104.6	TSL:2	c.-9-2601C>T		intron	N/A	ENSP00000364245.2

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

African (AFR) AF: 0.205 AC: 8506 AN: 41472

American (AMR) AF: 0.117 AC: 1796 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.155 AC: 804 AN: 5176

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4820

European-Finnish (FIN) AF: 0.0456 AC: 483 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4878 AN: 67998

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.0997 Hom.: 3139

Bravo AF: 0.130

Asia WGS AF: 0.243 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.76
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs408359; hg19: chr6-32141883;