4-83544578-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032717.5(GPAT3):c.184A>G(p.Ile62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,614,108 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I62S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00091 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (4 hom.)
• Consequence: GPAT3 NM_032717.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002964586).
• BP6: Variant 4-83544578-A-G is Benign according to our data. Variant chr4-83544578-A-G is described in ClinVar as [Benign]. Clinvar id is 784488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAT3	NM_032717.5	c.184A>G	p.Ile62Val	missense_variant	2/12	ENST00000264409.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPAT3	ENST00000264409.5	c.184A>G	p.Ile62Val	missense_variant	2/12	1	NM_032717.5	P1

Frequencies

GnomAD3 genomes AF: 0.000894 AC: 136 AN: 152204 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00693

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00156 AC: 393 AN: 251374 Hom.: 2 AF XY: 0.00117 AC XY: 159 AN XY: 135850

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.000870

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000417 AC: 609 AN: 1461786 Hom.: 4 Cov.: 31 AF XY: 0.000382 AC XY: 278 AN XY: 727192

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00165

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152322 Hom.: 2 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74484

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.00138

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00114 AC: 138

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.3
Dann	Benign	0.64
DEOGEN2	Benign	0.014	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.20	T;.;.
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.12
MVP		0.11
MPC		0.088
ClinPred		0.0013	T
GERP RS		-2.4
Varity_R		0.029
gMVP		0.20

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

Other links and lift over

dbSNP: rs186766919; hg19: chr4-84465731; COSMIC: COSV104579437;