8-6730729-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018361.5(AGPAT5):c.308A>G(p.Asp103Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AGPAT5 NM_018361.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPAT5	NM_018361.5	c.308A>G	p.Asp103Gly	missense_variant	3/8	ENST00000285518.11
AGPAT5	XM_047421940.1	c.308A>G	p.Asp103Gly	missense_variant	3/5
AGPAT5	XM_047421938.1	c.-146A>G		5_prime_UTR_variant	2/7
AGPAT5	XM_047421939.1	c.-146A>G		5_prime_UTR_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT5	ENST00000285518.11	c.308A>G	p.Asp103Gly	missense_variant	3/8	1	NM_018361.5	P1
AGPAT5	ENST00000518327.1	c.195+21842A>G		intron_variant		1
AGPAT5	ENST00000523234.5	c.238A>G	p.Thr80Ala	missense_variant, NMD_transcript_variant	2/7	5
AGPAT5	ENST00000523586.1	c.*240A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jul 14, 2021

The c.308A>G (p.D103G) alteration is located in exon 3 (coding exon 3) of the AGPAT5 gene. This alteration results from a A to G substitution at nucleotide position 308, causing the aspartic acid (D) at amino acid position 103 to be replaced by a glycine (G). 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	0.89
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
Cadd	Uncertain	25
Dann	Benign	0.71
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.11	T
Polyphen		0.95	P
Vest4		0.95
MutPred		0.65		Loss of catalytic residue at D103 (P = 0.043);
MVP		0.99
MPC		0.030
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.72
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr8-6588250;