chr4-83581577-A-G

Position:

• chr4-83581577-A-G

Variant summary

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

The NM_032717.5(GPAT3):​c.224A>G​(p.Asp75Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.76

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAT3	NM_032717.5	c.224A>G	p.Asp75Gly	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.224A>G	p.Asp75Gly	missense_variant	3/12	1	NM_032717.5	ENSP00000264409	P1
GPAT3	ENST00000395226.6	c.224A>G	p.Asp75Gly	missense_variant	4/13	1		ENSP00000378651	P1
GPAT3	ENST00000611707.4	c.224A>G	p.Asp75Gly	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

Mar 19, 2024

The c.224A>G (p.D75G) 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 224, causing the aspartic acid (D) at amino acid position 75 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	0.077
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;.;.
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	.;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.92	P;P;P
Vest4		0.60
MutPred		0.42		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		0.83
MPC		0.24
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.54
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr4-84502730;