Genetic Variant NM_006411.4:c.*282G>A (chr6-32168994-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

6 publications found

Variant links:

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]

AGPAT1 links:

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]

PPT2-EGFL8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT1	NM_006411.4 link	c.*282G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000375107.8	NP_006402.1	Q99943A0A024RCV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPAT1	ENST00000375107.8 link	c.*282G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_006411.4	ENSP00000364248.3		Q99943
PPT2-EGFL8	ENST00000422437.5 link	n.*1379-299C>T		intron_variant	Intron 17 of 20	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2289

AN:

151956

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0155

AC XY:

2853

AN XY:

183702

show subpopulations

African (AFR)

AF:

0.00385

AC:

AN:

11182

American (AMR)

AF:

0.00768

AC:

118

AN:

15358

Ashkenazi Jewish (ASJ)

AF:

0.00480

AC:

AN:

11672

East Asian (EAS)

AF:

0.00

AC:

AN:

27126

South Asian (SAS)

AF:

0.000428

AC:

AN:

28070

European-Finnish (FIN)

AF:

0.0187

AC:

444

AN:

23768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1654

European-Non Finnish (NFE)

AF:

0.0224

AC:

4829

AN:

215222

Other (OTH)

AF:

0.0133

AC:

286

AN:

21574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

266

531

797

1062

1328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0151

AC:

2289

AN:

152074

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1077

AN XY:

74348

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0246

AC:

1672

AN:

67966

Other (OTH)

AF:

0.0138

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

223

334

446

557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0213

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over