chr4-83598692-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_032717.5(GPAT3):c.1174G>C(p.Ala392Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,469,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00073 ( 0 hom., cov: 26)
Exomes 𝑓: 0.00072 ( 1 hom. )
Consequence
GPAT3
NM_032717.5 missense
NM_032717.5 missense
Scores
7
7
2
Clinical Significance
Conservation
PhyloP100: 9.79
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31179875).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPAT3 | NM_032717.5 | c.1174G>C | p.Ala392Pro | missense_variant | 11/12 | ENST00000264409.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPAT3 | ENST00000264409.5 | c.1174G>C | p.Ala392Pro | missense_variant | 11/12 | 1 | NM_032717.5 | P1 | |
GPAT3 | ENST00000395226.6 | c.1174G>C | p.Ala392Pro | missense_variant | 12/13 | 1 | P1 | ||
GPAT3 | ENST00000611707.4 | c.1174G>C | p.Ala392Pro | missense_variant | 12/13 | 5 | P1 | ||
GPAT3 | ENST00000509044.1 | n.164G>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000731 AC: 95AN: 129972Hom.: 0 Cov.: 26
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000409 AC: 102AN: 249502Hom.: 0 AF XY: 0.000408 AC XY: 55AN XY: 134966
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GnomAD4 exome AF: 0.000720 AC: 965AN: 1339580Hom.: 1 Cov.: 35 AF XY: 0.000713 AC XY: 474AN XY: 664794
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GnomAD4 genome ? AF: 0.000731 AC: 95AN: 130018Hom.: 0 Cov.: 26 AF XY: 0.000863 AC XY: 53AN XY: 61428
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2022 | The c.1174G>C (p.A392P) alteration is located in exon 11 (coding exon 11) of the GPAT3 gene. This alteration results from a G to C substitution at nucleotide position 1174, causing the alanine (A) at amino acid position 392 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
0.57
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at