NM_032717.5:c.437T>C

Variant names:

• chr4-83581790-T-C
• rs953768221
• NM_032717.5:c.437T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032717.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAT3	NM_032717.5	MANE Select	c.437T>C	p.Val146Ala	missense	Exon 3 of 12	NP_116106.2
	GPAT3	NM_001256421.1		c.437T>C	p.Val146Ala	missense	Exon 4 of 13	NP_001243350.1	Q53EU6
	GPAT3	NM_001256422.1		c.437T>C	p.Val146Ala	missense	Exon 4 of 13	NP_001243351.1	Q53EU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAT3	ENST00000264409.5	TSL:1 MANE Select	c.437T>C	p.Val146Ala	missense	Exon 3 of 12	ENSP00000264409.4	Q53EU6
	GPAT3	ENST00000395226.6	TSL:1	c.437T>C	p.Val146Ala	missense	Exon 4 of 13	ENSP00000378651.2	Q53EU6
	GPAT3	ENST00000611707.4	TSL:5	c.437T>C	p.Val146Ala	missense	Exon 4 of 13	ENSP00000482571.1	Q53EU6

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.095
Sift	Benign	0.36	T
Sift4G	Benign	0.35	T
Polyphen		0.70	P
Vest4		0.71
MutPred		0.49		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
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs953768221; hg19: chr4-84502943;