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GeneBe

8-6708754-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018361.5(AGPAT5):c.86T>A(p.Val29Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AGPAT5
NM_018361.5 missense

Scores

4
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36
Variant links:
Genes affected
AGPAT5 (HGNC:20886): (1-acylglycerol-3-phosphate O-acyltransferase 5) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. A pseudogene of this gene is present on the Y chromosome. [provided by RefSeq, Aug 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGPAT5NM_018361.5 linkuse as main transcriptc.86T>A p.Val29Glu missense_variant 1/8 ENST00000285518.11
AGPAT5XM_047421940.1 linkuse as main transcriptc.86T>A p.Val29Glu missense_variant 1/5
AGPAT5XM_047421938.1 linkuse as main transcriptc.-298T>A 5_prime_UTR_variant 1/7
AGPAT5XM_047421939.1 linkuse as main transcriptc.-430T>A 5_prime_UTR_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGPAT5ENST00000285518.11 linkuse as main transcriptc.86T>A p.Val29Glu missense_variant 1/81 NM_018361.5 P1
AGPAT5ENST00000518327.1 linkuse as main transcriptc.63T>A p.Arg21= synonymous_variant 1/31
AGPAT5ENST00000523234.5 linkuse as main transcriptc.86T>A p.Val29Glu missense_variant, NMD_transcript_variant 1/75

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456424
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
724810
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

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 submitterclinical testingAmbry GeneticsOct 20, 2023The c.86T>A (p.V29E) alteration is located in exon 1 (coding exon 1) of the AGPAT5 gene. This alteration results from a T to A substitution at nucleotide position 86, causing the valine (V) at amino acid position 29 to be replaced by a glutamic acid (E). 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
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
Cadd
Pathogenic
26
Dann
Uncertain
0.98
DEOGEN2
Uncertain
0.51
D
Eigen
Benign
0.061
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Pathogenic
0.86
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
0.038
D
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.55
Sift
Benign
0.032
D
Sift4G
Uncertain
0.022
D
Polyphen
0.72
P
Vest4
0.58
MutPred
0.68
Loss of MoRF binding (P = 0.1109);
MVP
0.95
MPC
0.047
ClinPred
0.96
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.83

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: chr8-6566275; API