4-83598692-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4

The NM_032717.5(GPAT3):c.1174G>C(p.Ala392Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,469,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00072 ( 1 hom. )

Consequence

GPAT3
NM_032717.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.79

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.31179875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAT3	NM_032717.5 linkuse as main transcript	c.1174G>C	p.Ala392Pro	missense_variant	11/12	ENST00000264409.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPAT3	ENST00000264409.5 linkuse as main transcript	c.1174G>C	p.Ala392Pro	missense_variant	11/12	1	NM_032717.5	P1
GPAT3	ENST00000395226.6 linkuse as main transcript	c.1174G>C	p.Ala392Pro	missense_variant	12/13	1		P1
GPAT3	ENST00000611707.4 linkuse as main transcript	c.1174G>C	p.Ala392Pro	missense_variant	12/13	5		P1
GPAT3	ENST00000509044.1 linkuse as main transcript	n.164G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000731

AC:

AN:

129972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000205

Gnomad AMI

AF:

0.0195

Gnomad AMR

AF:

0.000683

Gnomad ASJ

AF:

0.000301

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000536

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000886

Gnomad OTH

AF:

0.00111

GnomAD3 exomes

AF:

0.000409

AC:

102

AN:

249502

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

134966

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000879

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000805

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000720

AC:

965

AN:

1339580

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

474

AN XY:

664794

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.0000985

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000414

Gnomad4 NFE exome

AF:

0.000881

Gnomad4 OTH exome

AF:

0.000457

GnomAD4 genome

AF:

0.000731

AC:

AN:

130018

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

AN XY:

61428

show subpopulations

Gnomad4 AFR

AF:

0.000205

Gnomad4 AMR

AF:

0.000682

Gnomad4 ASJ

AF:

0.000301

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000536

Gnomad4 NFE

AF:

0.000886

Gnomad4 OTH

AF:

0.00110

Alfa

AF:

0.000685

Hom.:

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000486

AC:

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

Jan 10, 2022

The c.1174G>C (p.A392P) alteration is located in exon 11 (coding exon 11) of the GPAT3 gene. This alteration results from a G to C substitution at nucleotide position 1174, causing the alanine (A) at amino acid position 392 to be replaced by a proline (P). 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

1.0

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.32

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;.;.

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

3.2

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.96

MVP

0.96

MPC

0.57

ClinPred

0.81

GERP RS

5.5

Varity_R

0.94

gMVP

0.93

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