Variant 21-43959715-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000291572.13(AGPAT3):c.34G>A(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

AGPAT3
ENST00000291572.13 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13770974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT3	NM_020132.5 linkuse as main transcript	c.34G>A	p.Val12Met	missense_variant	3/10	ENST00000291572.13	NP_064517.1	Q9NRZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT3	ENST00000291572.13 linkuse as main transcript	c.34G>A	p.Val12Met	missense_variant	3/10	1	NM_020132.5	ENSP00000291572.8		Q9NRZ7-1
ENSG00000288593	ENST00000674444.1 linkuse as main transcript	c.*42G>A		downstream_gene_variant				ENSP00000501503.1		A0A9L9P0W8

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251270

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1461474

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2023

The c.34G>A (p.V12M) alteration is located in exon 3 (coding exon 1) of the AGPAT3 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;.;T;T;T;T;T;.;T;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.85

.;D;.;.;D;.;.;.;D;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;.;L;L;.;L;L;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.62

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.082

Sift

Uncertain

0.010

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D;D;D;D;T;D;T;D

Polyphen

0.46

P;.;P;P;.;P;P;.;.;.;P

Vest4

0.10

MutPred

0.41

Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);

MVP

0.22

MPC

0.94

ClinPred

0.10

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.039

gMVP

0.31

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