4-83581790-T-C

Position:

• chr4-83581790-T-C

Variant summary

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

The NM_032717.5(GPAT3):​c.437T>C​(p.Val146Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPAT3 NM_032717.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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.437T>C	p.Val146Ala	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.437T>C	p.Val146Ala	missense_variant	3/12	1	NM_032717.5	ENSP00000264409	P1
GPAT3	ENST00000395226.6	c.437T>C	p.Val146Ala	missense_variant	4/13	1		ENSP00000378651	P1
GPAT3	ENST00000611707.4	c.437T>C	p.Val146Ala	missense_variant	4/13	5		ENSP00000482571	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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.437T>C (p.V146A) alteration is located in exon 3 (coding exon 3) of the GPAT3 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the valine (V) at amino acid position 146 to be replaced by an alanine (A). 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	0.19
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.061	T;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T;.;.
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.095
Sift	Benign	0.36	.;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.70	P;P;P
Vest4		0.71
MutPred		0.49		Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);
MVP		0.60
MPC		0.18
ClinPred		0.69	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.55

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: rs953768221; hg19: chr4-84502943;