Variant 9-136673873-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006412.4(AGPAT2):c.716C>G(p.Ala239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

Variant links:

Genes affected

AGPAT2 (HGNC:325): (1-acylglycerol-3-phosphate O-acyltransferase 2) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

AGPAT2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32688123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGPAT2	NM_006412.4 linkuse as main transcript	c.716C>G	p.Ala239Gly	missense_variant	6/6	ENST00000371696.7	NP_006403.2
AGPAT2	NM_001012727.2 linkuse as main transcript	c.620C>G	p.Ala207Gly	missense_variant	5/5		NP_001012745.1
AGPAT2	XM_047422636.1 linkuse as main transcript	c.407C>G	p.Ala136Gly	missense_variant	6/6		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.716C>G	p.Ala239Gly	missense_variant	6/6	1	NM_006412.4	ENSP00000360761	P1	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.620C>G	p.Ala207Gly	missense_variant	5/5	1		ENSP00000360759		O15120-2
AGPAT2	ENST00000472820.1 linkuse as main transcript	n.644C>G		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000429

AC:

AN:

233002

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126638

show subpopulations

Gnomad AFR exome

AF:

0.0000677

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721156

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Benign

3.6

DANN

Benign

0.96

DEOGEN2

Benign

0.14

.;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.72

T;.;T

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.7

.;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.71

N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.087

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.94

P;P;P

Vest4

0.13

MutPred

0.53

.;Loss of stability (P = 0.0092);Loss of stability (P = 0.0092);

MVP

0.96

MPC

0.16

ClinPred

0.11

GERP RS

2.0

Varity_R

0.049

gMVP

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over