Genetic Variant AGPAT3:p.Phe11Phe (chr21-43959714-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001369881.1(AGPAT3):c.-42C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,613,748 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 43 hom. )

Consequence

AGPAT3
NM_001369881.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

AGPAT3 (HGNC:326): (1-acylglycerol-3-phosphate O-acyltransferase 3) The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AGPAT3 links:

ENSG00000288593 (HGNC:):

ENSG00000288593 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 21-43959714-C-T is Benign according to our data. Variant chr21-43959714-C-T is described in ClinVar as [Benign]. Clinvar id is 2652727.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT3	NM_020132.5 link	c.33C>T	p.Phe11Phe	synonymous_variant	Exon 3 of 10	ENST00000291572.13	NP_064517.1	Q9NRZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPAT3	ENST00000291572.13 link	c.33C>T	p.Phe11Phe	synonymous_variant	Exon 3 of 10	1	NM_020132.5	ENSP00000291572.8		Q9NRZ7-1
ENSG00000288593	ENST00000674444.1 link	c.*41C>T		downstream_gene_variant				ENSP00000501503.1		A0A9L9P0W8

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

507

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00412

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00496

AC:

1247

AN:

251240

AF XY:

0.00549

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.000924

Gnomad FIN exome

AF:

0.00335

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00478

AC:

6988

AN:

1461454

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3717

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.00221

AC:

AN:

44716

Gnomad4 ASJ exome

AF:

0.0182

AC:

476

AN:

26120

Gnomad4 EAS exome

AF:

0.000378

AC:

AN:

39694

Gnomad4 SAS exome

AF:

0.0123

AC:

1060

AN:

86248

Gnomad4 FIN exome

AF:

0.00350

AC:

186

AN:

53124

Gnomad4 NFE exome

AF:

0.00427

AC:

4752

AN:

1111930

Gnomad4 Remaining exome

AF:

0.00512

AC:

309

AN:

60378

Heterozygous variant carriers

482

963

1445

1926

2408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.00334

AC:

508

AN:

152294

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000770

AC:

0.000770416

AN:

0.000770416

Gnomad4 AMR

AF:

0.00150

AC:

0.00150268

AN:

0.00150268

Gnomad4 ASJ

AF:

0.0173

AC:

0.0172811

AN:

0.0172811

Gnomad4 EAS

AF:

0.000771

AC:

0.00077101

AN:

0.00077101

Gnomad4 SAS

AF:

0.0141

AC:

0.0140728

AN:

0.0140728

Gnomad4 FIN

AF:

0.00263

AC:

0.00263405

AN:

0.00263405

Gnomad4 NFE

AF:

0.00413

AC:

0.00413162

AN:

0.00413162

Gnomad4 OTH

AF:

0.00473

AC:

0.00473485

AN:

0.00473485

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00494

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AGPAT3: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over