Variant 4-83597508-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032717.5(GPAT3):c.989C>T(p.Ala330Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 1,549,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

GPAT3
NM_032717.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83

Variant links:

Genes affected

GPAT3 (HGNC:28157): (glycerol-3-phosphate acyltransferase 3) This gene encodes a member of the lysophosphatidic acid acyltransferase protein family. The encoded protein is an enzyme which catalyzes the conversion of glycerol-3-phosphate to lysophosphatidic acid in the synthesis of triacylglycerol. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2012]

GPAT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAT3	NM_032717.5 linkuse as main transcript	c.989C>T	p.Ala330Val	missense_variant	9/12	ENST00000264409.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPAT3	ENST00000264409.5 linkuse as main transcript	c.989C>T	p.Ala330Val	missense_variant	9/12	1	NM_032717.5	P1
GPAT3	ENST00000395226.6 linkuse as main transcript	c.989C>T	p.Ala330Val	missense_variant	10/13	1		P1
GPAT3	ENST00000611707.4 linkuse as main transcript	c.989C>T	p.Ala330Val	missense_variant	10/13	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151904

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1397168

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000373

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 13, 2023

The c.989C>T (p.A330V) alteration is located in exon 9 (coding exon 9) of the GPAT3 gene. This alteration results from a C to T substitution at nucleotide position 989, causing the alanine (A) at amino acid position 330 to be replaced by a valine (V). 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

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.62

D;D;D

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;.;.

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Uncertain

0.78

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.83

MutPred

0.75

Loss of glycosylation at T325 (P = 0.0326);Loss of glycosylation at T325 (P = 0.0326);Loss of glycosylation at T325 (P = 0.0326);

MVP

0.98

MPC

0.25

ClinPred

0.99

GERP RS

5.3

Varity_R

0.71

gMVP

0.82

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