Variant 8-6708851-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018361.5(AGPAT5):c.183G>T(p.Met61Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

AGPAT5
NM_018361.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGPAT5	NM_018361.5 linkuse as main transcript	c.183G>T	p.Met61Ile	missense_variant	1/8	ENST00000285518.11
AGPAT5	XM_047421940.1 linkuse as main transcript	c.183G>T	p.Met61Ile	missense_variant	1/5
AGPAT5	XM_047421938.1 linkuse as main transcript	c.-201G>T		5_prime_UTR_variant	1/7
AGPAT5	XM_047421939.1 linkuse as main transcript	c.-333G>T		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.183G>T	p.Met61Ile	missense_variant	1/8	1	NM_018361.5	P1
AGPAT5	ENST00000518327.1 linkuse as main transcript	c.160G>T	p.Gly54Cys	missense_variant	1/3	1
AGPAT5	ENST00000523234.5 linkuse as main transcript	c.183G>T	p.Met61Ile	missense_variant, NMD_transcript_variant	1/7	5
AGPAT5	ENST00000523586.1 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000816

AC:

AN:

245166

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457600

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000314

Hom.:

ExAC

AF:

0.00000824

AC:

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 09, 2024

The c.183G>T (p.M61I) alteration is located in exon 1 (coding exon 1) of the AGPAT5 gene. This alteration results from a G to T substitution at nucleotide position 183, causing the methionine (M) at amino acid position 61 to be replaced by an isoleucine (I). 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

0.60

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

0.10

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.92

M_CAP

Pathogenic

0.30

MetaRNN

Uncertain

0.62

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.52

Sift

Benign

0.092

Sift4G

Benign

0.32

Polyphen

0.029

Vest4

0.68

MutPred

0.67

Loss of catalytic residue at V57 (P = 0.0601);

MVP

0.88

MPC

0.025

ClinPred

0.76

GERP RS

3.9

Varity_R

0.67

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over