chr4-83581580-A-G

Position:

• chr4-83581580-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032717.5(GPAT3):​c.227A>G​(p.Glu76Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPAT3 NM_032717.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

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 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=0.12587649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAT3	NM_032717.5	c.227A>G	p.Glu76Gly	missense_variant	3/12	ENST00000264409.5	NP_116106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPAT3	ENST00000264409.5	c.227A>G	p.Glu76Gly	missense_variant	3/12	1	NM_032717.5	ENSP00000264409	P1
GPAT3	ENST00000395226.6	c.227A>G	p.Glu76Gly	missense_variant	4/13	1		ENSP00000378651	P1
GPAT3	ENST00000611707.4	c.227A>G	p.Glu76Gly	missense_variant	4/13	5		ENSP00000482571	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.227A>G (p.E76G) alteration is located in exon 3 (coding exon 3) of the GPAT3 gene. This alteration results from a A to G substitution at nucleotide position 227, causing the glutamic acid (E) at amino acid position 76 to be replaced by a glycine (G). 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	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.0058
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.73	T;.;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	0.61	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	.;N;N
REVEL	Benign	0.075
Sift	Benign	0.11	.;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.19
MutPred		0.22		Gain of glycosylation at S77 (P = 0.0017);Gain of glycosylation at S77 (P = 0.0017);Gain of glycosylation at S77 (P = 0.0017);
MVP		0.53
MPC		0.13
ClinPred		0.73	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84502733;