chr4-83594875-A-T

Position:

• chr4-83594875-A-T

Variant summary

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

The NM_032717.5(GPAT3):​c.769A>T​(p.Ile257Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: 0.495

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.769A>T	p.Ile257Phe	missense_variant	7/12	ENST00000264409.5	NP_116106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPAT3	ENST00000264409.5	c.769A>T	p.Ile257Phe	missense_variant	7/12	1	NM_032717.5	ENSP00000264409	P1
GPAT3	ENST00000395226.6	c.769A>T	p.Ile257Phe	missense_variant	8/13	1		ENSP00000378651	P1
GPAT3	ENST00000611707.4	c.769A>T	p.Ile257Phe	missense_variant	8/13	5		ENSP00000482571	P1
GPAT3	ENST00000513683.1	n.167A>T		non_coding_transcript_exon_variant	3/3	5

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

Sep 17, 2021

The c.769A>T (p.I257F) alteration is located in exon 7 (coding exon 7) of the GPAT3 gene. This alteration results from a A to T substitution at nucleotide position 769, causing the isoleucine (I) at amino acid position 257 to be replaced by a phenylalanine (F). 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	0.10
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.39	T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D;.;.
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.28	N;N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.25	.;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.63	P;P;P
Vest4		0.67
MutPred		0.59		Gain of catalytic residue at I257 (P = 0.0638);Gain of catalytic residue at I257 (P = 0.0638);Gain of catalytic residue at I257 (P = 0.0638);
MVP		0.76
MPC		0.33
ClinPred		0.32	T
GERP RS		0.45
Varity_R		0.12
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84516028;