Variant 8-6708867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018361.5(AGPAT5):c.199G>A(p.Glu67Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,496 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: 6.9e-7 ( 0 hom. )

Consequence

AGPAT5
NM_018361.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20

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]

AGPAT5 links:

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ACMG classification

Classification made for transcript

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, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGPAT5	NM_018361.5 linkuse as main transcript	c.199G>A	p.Glu67Lys	missense_variant	1/8	ENST00000285518.11
AGPAT5	XM_047421940.1 linkuse as main transcript	c.199G>A	p.Glu67Lys	missense_variant	1/5
AGPAT5	XM_047421938.1 linkuse as main transcript	c.-185G>A		5_prime_UTR_variant	1/7
AGPAT5	XM_047421939.1 linkuse as main transcript	c.-317G>A		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AGPAT5	ENST00000285518.11 linkuse as main transcript	c.199G>A	p.Glu67Lys	missense_variant	1/8	1	NM_018361.5	P1
AGPAT5	ENST00000518327.1 linkuse as main transcript	c.176G>A	p.Arg59Gln	missense_variant	1/3	1
AGPAT5	ENST00000523234.5 linkuse as main transcript	c.199G>A	p.Glu67Lys	missense_variant, NMD_transcript_variant	1/7	5
AGPAT5	ENST00000523586.1 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, NMD_transcript_variant	1/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455496

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723818

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 20, 2023

The c.199G>A (p.E67K) alteration is located in exon 1 (coding exon 1) of the AGPAT5 gene. This alteration results from a G to A substitution at nucleotide position 199, causing the glutamic acid (E) at amino acid position 67 to be replaced by a lysine (K). 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

0.93

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.93

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0080

Sift4G

Benign

0.073

Polyphen

0.97

Vest4

0.79

MutPred

0.78

Gain of methylation at E67 (P = 0.0191);

MVP

0.95

MPC

0.063

ClinPred

0.99

GERP RS

3.9

Varity_R

0.77

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over