Variant 21-43959835-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020132.5(AGPAT3):c.154C>T(p.Arg52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,610,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

AGPAT3
NM_020132.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

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=0.07054487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT3	NM_020132.5 link	c.154C>T	p.Arg52Cys	missense_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.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 10	1	NM_020132.5	ENSP00000291572.8		Q9NRZ7-1
ENSG00000288593	ENST00000674444.1 link	c.*162C>T		downstream_gene_variant				ENSP00000501503.1		A0A9L9P0W8

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000264

AC:

AN:

246176

Hom.:

AF XY:

0.000262

AC XY:

AN XY:

133676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00115

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.000998

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000149

AC:

217

AN:

1458112

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

725504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000706

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000630

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.154C>T (p.R52C) alteration is located in exon 3 (coding exon 1) of the AGPAT3 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a cysteine (C). 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

0.21

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

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

Eigen

Benign

-0.017

Eigen_PC

Benign

0.094

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

.;D;.;.;D;.;.;.;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.071

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

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

M;.;M;M;.;M;M;.;.;M

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.1

N;D;N;N;D;N;N;D;D;N

REVEL

Benign

0.26

Sift

Uncertain

0.029

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

Sift4G

Benign

0.16

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

Polyphen

0.090

B;.;B;B;.;B;B;.;.;B

Vest4

0.89

MVP

0.54

MPC

1.2

ClinPred

0.10

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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