6-32169319-C-T

Variant names:

• chr6-32169319-C-T
• rs748794275
• NM_006411.4:c.809G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006411.4(AGPAT1):​c.809G>A​(p.Arg270Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,460,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: AGPAT1 NM_006411.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.309
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05008477).

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.809G>A	p.Arg270Gln	missense	Exon 7 of 7	NP_006402.1	A0A024RCV5
	AGPAT1	NM_001371437.1		c.821G>A	p.Arg274Gln	missense	Exon 7 of 7	NP_001358366.1
	AGPAT1	NM_001371438.1		c.809G>A	p.Arg270Gln	missense	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.809G>A	p.Arg270Gln	missense	Exon 7 of 7	ENSP00000364248.3	Q99943
	AGPAT1	ENST00000336984.6	TSL:1	c.809G>A	p.Arg270Gln	missense	Exon 7 of 7	ENSP00000337463.6	Q99943
	PPT2-EGFL8	ENST00000422437.5	TSL:5	n.*1405C>T		non_coding_transcript_exon	Exon 18 of 21	ENSP00000457534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 246360 AF XY: 0.0000372

Gnomad AFR exome AF: 0.0000663

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1460724 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726686

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111968

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000169 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.025	N
PhyloP100		0.31
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	0.71	T
Polyphen		0.0030	B
Vest4		0.076
MutPred		0.38		Loss of methylation at R270 (P = 0.0089)
MVP		0.41
MPC		1.3
ClinPred		0.040	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.76
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748794275; hg19: chr6-32137096;